Biological Properties

There are no known natural vectors for the recognized chrysoviruses PcV, PbV, Pc-fV, and Hv145SV. They are transmitted intracellularly during cell division and sporo-genesis (vertical transmission), and following hyphal anastomosis (cell fusion) between compatible fungal strains (horizontal transmission). Unlike the Penicillium chrysoviruses, which are associated with latent infections oftheir hosts, all other known chrysoviruses occur in mixed infections with other mycoviruses (or possibly...

DsRNA Viruses Infecting Eukaryotic Algae MpRV

Heterocapsa Circularisquama

The micromonas pusilla reovirus (MpRV, originally abbreviated as MpRNAV) is a dsRNA virus infecting the cosmopolitan picoprasinophyte M. pusilla (Figure 6). Figure 4 Transmission electron micrographs of intracellular crystalline array formation of HcRNAV (a) and negatively stained HcRNAV particles (b). Reprinted from Tomaru Y, Katanozaka N, Nishida K, et al. (2004) Isolation and characterization of two distinct types of HcRNAV, a single-stranded RNA virus infecting the bivalve-killing microalga...

Entero and Rhinovirus Genome Structures

Briefly, a viral protein (VPg), is covalently linked to the 5' end of the genome and followed by a nontranslated region, the 5' NTR (Figure 1(a)). A single, long, open reading frame (ORF) encodes a polyprotein of 2200 aa. The N-terminal domain of the polyprotein (P1) comprises the four capsid proteins, while the replicative proteins comprise the central domain (P2) and C-terminal domain (P3) of the polyprotein. The full-length translation product predicted by the single ORF is not observed...

Brief History of Hivaids

Although the first cases of acquired immune deficiency syndrome (AIDS) were recognized in the United States in 1981, phylogenetic analysis of human immunodeficiency virus (HIV) sequences suggest that HIV may have been initially transmitted to humans around 1930. By 1985, HIV had been identified in every region of the world and an estimated 1.5 million people were infected globally. Since then, unprecedented scientific advances have been made in the epidemiology, basic science, and treatment of...

Host Receptor Recognition Site

Animal viruses have to recognize a specific host cellular receptor for entry during infection. Host receptor binding is the initial step of virus life cycle and could be an effective target for preventing virus infection. Based on the atomic structure of animal viruses, it was found that the receptor recognition site is located in an area surrounded by hyper-variable regions of the antigenic sites. Usually, the area is in a depression (called the 'canyon') on the viral surface that may be...

MHCII Antigen Presentation

The MHC-II molecule is composed by two noncovalently bound transmembrane glycoprotein chains, a (34kDa) and b (29 kDa). Each chain has two domains and altogether form a four-domain heterodimer similar to the MHC-I molecule. a1 and b1 domains form the peptide-binding cleft resulting in a groove which is open at the ends, which is different from the MHC-I groove in which the extremes of the peptide are buried at the ends. Pep-tides that bind to MHC-II are larger than those that bind to MHC-I...

Satellite RNAs

CMV can also support satellite RNAs varying in size from 333 to 405 nt. These satellite RNAs are dependent upon CMV as the helper virus for both their replication and encapsidation, but have sequence similarity to the CMV RNAs limited to no more than 6-8 contiguous nt. More than 100 satellite variants have been found associated with over 65 isolates of CMV from both of the CMV subgroups. These satellite RNAs usually reduce the accumulation of the helper viruses and on most hosts also reduce the...

Apoptosis as an Antiviral Immune Response

Like all other living organisms, insects are constantly challenged by bacteria, fungi, and viruses. In vertebrate animals, immunity can be broken down into innate and adaptive immunity. Insects do not possess the adaptive immune response that is characteristic of vertebrates including antibodies and T cells. That does not mean, however, that insects are defenseless against invading microorganisms. Insects have robust innate immune systems that are in many ways similar to the innate immune...

Pathways of the CNS Invasion

Viruses have been shown to enter the nervous system both along nerves and from the blood. The first experimental studies of viral invasion employed rabies, herpes simplex, or polioviruses, all of which, under experimental circumstances, can penetrate the nervous system along peripheral nerves. The precise mechanisms of neural spread remained a mystery for many years, since it was thought that the axoplasm slowly oozed in an anterograde direction. It was proposed that virus might move in...

Host Immune Responses

An early nonspecific containment phase (innate immunity) and a later HSV-specific effector phase (adaptive immunity) contribute to protection. Natural killer (NK) cells and rapid production of IFN type I provide a threshold of resistance to HSV-1 infection and were associated with the natural resistance of certain mouse strains. In mice, IFNa p inhibit the onset of IE gene expression, limit virus spread into the nervous system, and activate NK cells. Dendritic cells (DCs) are required for...

EBVAssociated Diseases

Primary infection with EBV in childhood is usually asymptomatic but when delayed until adolescence or early adulthood can manifest clinically as IM, a self-limiting lymphoproliferative disease associated with the hyperexpansion of cytotoxic CD8+ T cells that are reactive to both lytic and latent cycle viral antigens. These reactivities are subsequently maintained in the CD8+ T-cell memory pool at high levels (up to 5 of circulating CD8+ T cells), even in individuals with no history of IM. The...

Avian Adenoviruses

Adenoviruses isolated from poultry and waterfowl were initially classified into genus Aviadenovirus. In addition to the criterion of host origin, aviadenoviruses can be distinguished from mastadenoviruses on the basis of a lack of the genus-common complement-fixing antigen. A large number of serotypes have been described from chicken. Some of these viruses have been isolated from other species as well. For example, strains serologically identical to CELO virus have also been found to cause...

Surveillance of Hivaids

The association of HIV AIDS with stigma makes surveillance of this infection especially difficult. The uniqueness and seriousness of this infection warrants a separate section. It is an example of the importance of tailoring surveillance to a specific serious infection if it becomes necessary to do so. In the UK and some other countries with data protection acts, HIV infection, as with other STIs, is not notifiable. Special confidential surveillance systems through clinicians and GUM clinics,...

How Many Herpesviruses Have Been Discovered

Since the publication ofthese methods, the number ofnovel herpesviruses discovered has risen very fast. Prior to writing this article, more than 200 potential herpesvirus species had been detected, belonging to more than 20 mammalian orders (Table 1). These are many more than currently accepted by the International Committee on Taxonomy of Viruses (ICTV), which lists some 120 herpesvirus species (Vlllth Report). Sequences of more than 160 herpesviruses are available under the taxonomy browser...

Pointof Care Tests

Point-of-care tests (POC tests) are becoming increasingly common in clinical practice. Most of them are based on easy-to-use lateral-flow or latex particle technology and are able to give the result in a few minutes. POC tests are nowadays available for antibody screening of an increasing number of virus infections (HIV, hepatitis C virus (HCV), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)). Some authorities still question the validity of POC tests for clinical...

Clinical Features and Pathology

Infections with HAV may produce a wide spectrum of manifestations ranging from silent infections, over icteric courses to fatal fulminant hepatitis. The acute icteric course of infection varies between common, over prolonged to relapsing hepatitis A. Persistent infections or chronic disease have not been described. The clinical presentation of the disease depends on the age of infection. The likelihood of having symptoms and the severity of the disease increases with the age of the patient....

Human Demographics and Behavior

In some cases, the emerging viruses themselves have contributed to other viruses emerging and reemerging in the population. This is especially true of human immunodeficiency virus (HIV), the cause of acquired immune deficiency syndrome (AIDS), which rapidly spread following its emergence in the early 1980s to infect more than 40 million people worldwide by the end of the twentieth century. Because of its severe effects on the immune system, the virus leads to numerous other infections in the...

Replication and Virion Assembly

Although there have been few biochemical studies ofviral DNA replication or protein synthesis, studies carried out with ascoviruses in vivo and in vitro show that progeny virions first appear about 12 h after infection. Virion assembly is initiated after the nucleus ruptures, and occurs prior to and during the cleavage of the cell into viral vesicles. The first recognizable structural component of the virion to form is the multilaminar layer of the inner particle. Based on its ultrastructure,...

Inducing Cell Mediated Immunity by Vaccination

In macaque models, vaccination with DNA plasmids or recombinant viruses bearing SIV SHIV antigenic inserts leads to significant attenuation of viremia after subsequent infection with the highly pathogenic X4-tropic hybrid isolate SHIV89.6P. Although they do not afford sterilizing immunity under any regimen tested thus far, such vaccines enable long-term suppression of viremia and prevent disease progression. Nonetheless, eventual escape of the challenge virus from CTL control after acquisition...

Other Clinical Sources of Data

Specific general practitioner (GP) surveillance systems are useful to provide data of epidemiological value for infections that are not notifiable, such as the common cold or chick-enpox (in UK). They are of course clinically based, but are nevertheless useful, and often surprisingly accurate, possibly because those GPs who subscribe to a surveillance system are motivated to do so. GP surveillance systems are often sentinel-based, that is, based on a sample of GPs in a country, region, or area....

Selecting the Best Target Antigens

The obvious advantage of CTL-based vaccines over those that aim to induce nAbs is that all HIV-1 proteins are targets for cellular immunity and some of these are considerably less tolerant of mutation than Env. CTLs escape mutations with a high cost to viral fitness and revert after transmission to a new host where the epitope is not targeted. Conversely, CTL epitopes restricted by common HLA class I alleles that are not critical to viral fitness will drive the accumulation of escape mutants in...

Expansion into Therapies for Other Viruses

A spin-off from this work with HIV has led to inhibitors of other families of viruses, particularly hepatitis B virus (HBV). Lamivudine and adefovir have become the treatments of choice for HBV. Meanwhile, there seemed to be progress discovering compounds active against picorna-viruses (which include rhinoviruses causing the common cold). These compounds bind into a pocket within the viral capsid. The best example is pleconaril although unacceptable side effects stopped its development....

Pathogenesis and Clinical Disease

HCV causes acute and chronic forms of viral hepatitis. Acute hepatitis resembles that caused by other agents of viral hepatitis, but overt symptoms are not as frequent, despite biochemical evidence of liver disease in most subjects and appearance of HCV RNA in the serum. HCV causes persistent infection in most infected individuals, who then have chronic hepatitis throughout their lives in the absence of treatment and who remain at risk for cirrhosis and hepatocellular carcinoma. The infection...

HCV Replication Cycle

HCV infection starts by binding the envelope glycoprotein E1 E2 complex on the surface of the virus particle to its cognate receptor(s) presumably leading to clathrin-mediated endocytosis and a subsequent fusion step from within an acidic endosomal compartment (Figure 3). Cellular factors implicated in virus binding and entry are glycosaminoglycans, scavenger receptor class B type 1 (SR-B1), CD81, and low-density lipoprotein (LDL) receptor. However, for most of these factors, the precise role...

Clinical Picture and Pathogenesis

Amur, Dobrava, Hantaan, Seoul, Puumala, and Saaremaa viruses all cause HFRS but the infections differ considerably in severity. All are characterized by acute-onset, fever, headache, abdominal pains, backache, temporary renal insufficiency (first oliguria, proteinuria, and increase in serum creatinine, and then polyuria), and thrombocytopenia, but the extent of hemorrhages (hematuria, petechiae, internal hemorrhages), requirement for dialysis treatment, hypotension, and case-fatality rates are...

Clinical Significance

Since their discovery, the question of a possible implication of anelloviruses in a particular disease is still a matter to debate. Historical presentation of TTV as associated with elevated transaminase levels in post-transfusion hepatitis of unknown etiology suggested that the virus was able to induce non-A G hepatitis. Therefore, TTV was suspected as a possible cause of some forms of acute and chronic hepatitis and fulminant liver failure, and could be involved in liver diseases. The...

Hepatitis D Virus

HDV merits a brief mention because of its particular association with HBV. As noted above, a novel antigen, termed delta, was discovered in patients with hepatitis B and this turned out to be the nucleocapsid protein of HDV. The HDV genome is a single-stranded circle of RNA that resembles the viroids and virusoids of plants it is believed to be replicated by the host RNA polymerase II, with cleavage and rejoining of the circle mediated by a ribozyme activity. Unlike the viroids and virusoids,...

HIV Prevention

Comprehensive and sustained prevention programs have been proven to reduce HIV transmission. Unfortunately, HIV prevention strategies have not reached the majority of people at high risk. The major challenge for prevention has been generating the political will and economic resources to effectively implement proven strategies that address issues such as sex, sexuality, and drug use. Behavioral interventions to promote safer sexual behavior are essential to reduce HIV transmission. In Zimbabwe,...

Scientific and Public Health Implications

Currently, a substantial fraction of human disease, with a presumed viral cause, goes without a clinical diagnosis. This is especially true for common ailments, such as upper respiratory tract infections, where despite advances in PCR assays, the etiology of 30-60 of infections remains unidentified. Without considering the complexities of diagnostic regulatory approvals, an unbiased DNA microarray approach to the detection of viral pathogens should substantially increase the number of...

HIV and Kidney Disease

Kidney disease related to AIDS was described as early as 1984 in reports from New York and Florida. Since then, a wide spectrum of acute and chronic renal syndromes has been reported. HIV-associated kidney disease was initially thought to occur late in the course of the infection, but it is now known that the kidneys may be involved in all the stages of HIV disease including acute infection. Renal glomerular and tubular epithelial cells may be directly infected by HIV. Effective therapies for...

Viral Regulators of the Mitochondrial Pathway

The mitochondrial cell death pathway is regulated by viral and cellular Bcl-2 proteins. Cellular Bcl-2 proteins are generally divided into three functional subgroups, anti-apoptotic (Bcl-2, Bcl-xL, Mcl-1, Bcl-w), pro-apoptotic Bcl-2 family members (Bax and Bak), and the more distantly related pro-apoptotic BH3-only proteins (Bad, Bid, and others). While these classifications generally apply, there are definitive examples where the endogenous functions of these proteins are opposite to expected....

Biophysical Properties

Dicistroviruses appear roughly spherical under the electron microscope in negative stained preparations with particle diameters of approximately 30 nm and no envelope (Figure 1). The mature virions contain three major structural proteins, VP1, VP2, and VP3 ofbetween 28 and 37 kDa, although taura syndrome virus (TSV) does appear to have one larger structural protein of 56 kDa. In many mature virion preparations, one or more minor structural components can be present which are larger than the...

Keterah Virus Also Known As Issyk Kul Virus

This virus was first isolated from Argas pusillus ticks collected from bats in Malaysia and from the bloods of those bats (Scotophilus temmencki), and has been isolated from ticks and mosquitoes that had fed on infected bats. It was subsequently isolated from pooled brain, liver, spleen, and kidney tissues of other bats in Kyrgyzstan and Tadzhikistan. The virus also was isolated from a staff member of a virology institute in Tadzhikistan who had contracted the infection during field work with...

Optimizing Antigens to Induce Abs with Antiviral Activity

The problem of inducing Abs of the correct specificities that will have protective roles in vivo has proved difficult to solve. It is clear from clinical trials conducted thus far that vaccination with native gp120, gp160, gp41, or Env peptides fails to induce nAbs against more than a handful of isolates. Therefore, improved strategies that aim to circumvent the immuno-evasive properties of Env are being developed. The use of consensus sequence Env reduces the antigenic distance between the...

The First Uncertain Steps

Following the discovery of antibiotics for treating bacterial infections, for several decades it was thought that 'safe' antiviral chemotherapy would be difficult if not impossible. The earliest antiviral compounds only emphasized the problems. Marboran was introduced in the early 1960s to treat smallpox and vaccinia its effectiveness was equivocal and its use short-lived. Amantadine and rimantadine were used to treat influenza with relatively little side effects but the influenza virus became...

Distribution Epidemiology and Transmission

In 1997, the identification of TTV DNA in the blood of Japanese patients with hepatitis of unknown etiology was the starting point of the research on this new group of viruses. Despite its initial identification in populations with liver disorders, further epidemiological studies not only identified the virus in populations with parenteral risk exposure, including intravenous drug users, hemophiliacs, or HIV infected patients, but also in populations without proven pathology like blood donors....

Genetic Makeup and Gene Structure

Vesiculoviruses exemplify one of the simplest genome architectures among the Mononegavirales. The entire CHPV genome has been sequenced and comparison with other vesiculoviruses has confirmed similar genetic makeup among vesiculoviruses. The Chandipura virus RNA genome comprises a 49-nt long leader sequence (l), followed by five transcriptional units coding for viral polypeptides separated by intergenic, nontranscribed spacer regions, and a short nontranscribed trailer sequence (t) arranged in...

Antiviral Prodrugs

The efficacies of several important antiviral drugs (including the nucleoside analogs acyclovir and penciclovir) are severely limited by poor oral bioavailability. One approach to this has been the synthesis of chemically modified derivatives that are rapidly converted to the nucleosides by the host metabolic enzymes. Valaciclovir, the prodrug for acyclovir, and famciclovir, the prodrug for penciclovir, are readily absorbed yielding high blood levels of the parent compound. Both are used widely...

Nucleic Acid Detection Assays

Direct demonstration of viral nucleic acids in clinical samples is an increasingly used technique for virus diagnosis. Using the polymerase chain reaction (PCR) with specific primers, viral sequences can be rapidly multiplied and identified. These techniques are largely replacing classical virus isolation. They are rapid to perform and in many cases more sensitive than virus isolation or antigen detection methods making earlier diagnosis possible. They have proved particularly valuable for the...

The Hepatitis B Vaccines

The hepatitis B vaccines contain HBsAg and are given via an intramuscular injection to stimulate a protective anti-HBs response. The first-generation (so-called 'plasma derived') vaccine was produced by purifying HBsAg from donated blood. Despite some worries that blood-borne viruses (particularly human immunodeficiency virus (HIV)) potentially might contaminate particular batches, this method of vaccine production is safe provided that manufacturing protocols, including steps that inactivate...

Western Europe

In the 1980s, HIV spread widely among men who had sex with men and injection-drug users in Western Europe. Subsequent prevention programs have had success in reducing the incidence of HIV in these risk groups although the HIV prevalence in injection-drug users in Southern Europe remains high. The major modes of HIV transmission are now unprotected heterosexual sex (56 ), unsafe sex between men (35 ), and injection drug use (8 ). Although heterosexual transmission has emerged as an important...

Structure and Replication

The structure and replication of the flaviviruses have served for many years as a model for the entire family, since the first report of the genomic sequence for yellow fever virus in 1985. The use of molecular clones, together with the ease of propagating most of these viruses in cell lines in vitro, and the advent of modern expression systems for production and purification of viral proteins, have facilitated progress for understanding the molecular biology of the family. A number of...

Introduction

Since the discovery of HIV-1, the causative agent of AIDS in 1983, researchers have attempted to develop a prophylactic vaccine to control the pandemic. Early attempts to achieve protective immunity made use of recombinant viral envelope glycoproteins (Env) to attempt to induce neutralizing antibody (nAb) responses. To date such approaches have not been successful, probably due to the inability of such subunit proteins to induce antibody (Ab) responses capable of cross-neutralizing the...

Clinical Features

Nonspecific, flu-like symptoms such as fever, chills, and malaise appear abruptly in infected individuals after an incubation period that ranges from 2 to 21 days, but on average lasts 4-10 days. Subsequently, multisystemic symptoms such as prostration, anorexia, vomiting, chest pain, and shortness of breath develop. Macropapular rash associated with varying degrees of erythema may also occur and is a valuable differential diagnostic feature. At the peak of the disease, vascular dysfunction...

Concluding Remarks

Co-evolution of certain hosts and pathogens for millions of years has resulted in a fine-tuned equilibrium that enables survival of both. Antigen presentation is one of the critical elements in this balance. While antigen presentation is an essential process for long-term effective host defense, targeting APCs represents a common maneuver of many viruses to avoid host surveillance and establish a chronic or persistent infection. A major challenge in biomedical research is to thwart microbial...

Symptoms and Yield Losses

The symptoms induced by TYLCV are typically a leaf curling of the leaves with different levels of yellowing (Figure 2). However in a single field of infected tomato plants a variety of symptoms can be observed from green to purple leaf curling, thickening of the veins and the stems, and various levels of stunting. In some instances, the leaf surface is reduced a minimum, with large veins and thick lamina. When plants are infected at an early stage, the plant fail to produce fruits and will stay...

Host Response to Infection

There are no detailed studies of the immune response of finfish to infection by aquareoviruses but, from observations that have been reported, it is clear that cellular and humoral immune reactions are stimulated. While not consistent, local infiltration of host inflammatory cells, particularly in the liver of infected fish, has been observed during aquareovirus infections. Moreover, in studies in which sera have been collected from infected fish, specific neutralization titers of > 1 4000...

Regulatory Viral RNAs and RNABinding Proteins

Early recognition of several viruses is mediated by PRRs and results in the activation of interferon and NF-kB. Recent advances have been made in this area through the discovery of RIG-I and Mda5 as well as their downstream signaling partner, the CARD-containing mito-chondrial antiviral signaling protein (MAVS). The protease NS3 4A from the flavivirus hepatitis C virus (HCV) cleaves and inactivates MAVS, thereby short-circuiting virus recognition and signaling through the CARD. Meanwhile, the...

Death Receptor Signaling

Death-inducing receptors on the cell surface can be placed into two subgroups, one containing Fas CD95 and the other containing tumor necrosis factor receptor 1 (TNFR1). Fas recruits caspase-8 to directly and potently activate cell death. TNFR1 recruits different factors to form a distinct complex to inefficiently induce apoptosis or to activate other cellular signaling pathways. Binding of Fas ligand (FasL) to Fas, or binding of TRAIL to death receptors 4 and 5 (DR4 and DR5), triggers the...

Antigen Presenting Cells

For initiation of an immune response, naive T cells need to be activated or 'primed'. For that, they require both the recognition ofthe specific MHC peptide complex (signal 1) and simultaneous co-stimulation (signal 2). Although all nucleated cells express MHC-I and can potentially display MHC-I microbial peptide complexes after infection, only a specialized group of leukocytes, named APCs, expresses both MHC-I and MHC-II as well as co-stimulatory molecules. The best-characterized...

Disease symptoms and yield losses

Symptomatic tomato plants in open field and greenhouses exhibit interveinal yellowing in older leaves, followed by generalized yellowing. Symptoms can be confused with nutritional disorders (i.e., magnesium deficiency), pesticide toxicity, or natural senescence as older leaves may also turn red. Necrosis and occasional upward rolling of the leaves have also been reported. On the whole, infected plants are less vigorous and with fruits that may show delayed ripening. There is no information on...

Important Classes of Antiviral Targets and Compounds

The major targets and compounds are illustrated in Figure 1. Currently, there are no major drugs which prevent virus attaching to the host cell. The problem has been illustrated by the picornavirus capsid-binding compounds such as pleconaril. Other compounds are being tried for HIV but with little success so far. It seems that many sites on the surface of a virus can undergo changes without great loss of viral viability the compounds present too low a genetic barrier (see below). To date, only...

Geographical Distribution

The tomato yellow leaf curl virus (TYLCV) was originally reported isolated from Israel and was described in the 1960s, mostly infecting tomatoes and causing very severe symptoms and huge losses. In Spain and Italy, tomato production increased considerably in the 1980s, and closely related viruses were identified in these countries which were first mistakenly identified as new strains of TYLCVs, although the Israeli virus was subsequently identified in these countries. Furthermore, recombinants...

Phylogenetic Relationships

The relationships detected between the genera within the family and those between members of the family Flexiviridae and other viruses are dependent on the genome region used for analysis. This probably indicates that the viruses have arisen from reassortment of entire genes (or blocks of genes). These relationships are summarized below. A dendrogram based on the nucleotide sequence of the replication proteins (Figure 3) supports the taxonomic division of the family Flexiviridae into genera and...

Antiviral Combination Therapy

The problem of antiviral resistance led directly to the introduction of antiviral combination therapy as a crucial feature to control chronic virus infections, notably those caused by HIV and probably will be with HBV and HCV. Initially, there was much opposition to the introduction of antiviral combinations, probably best explained by an underlying fear of enhanced toxicity this was the problem that dominated the early phase of HIV therapy but eased as newer, better tolerated drugs became...

Future Perspectives

As present, too little is known about ascoviruses to assess whether they are or will turn out to be of economic importance. Their poor infectivity per os makes it highly unlikely they will ever be developed as viral insecticides, especially given the successful advent of insect-resistant transgenic crops. However, as more entomologists become familiar with the disease caused by ascoviruses, it may be shown that in habitats rarely treated with chemical insecticides, such as transgenic crops,...

NPVSpecific Genes

The lepidopteran NPVs have 28 genes that are specific to all members of this genus and a further 13 genes specific to group II NPVs and 21 genes specific to group I NPVs (Figure 4). A number of these genes have been characterized and are known to impart specific functionality on these viruses but many remain to be investigated to determine their role in NPV biology. See also Baculoviruses Apoptosis Inhibitors Baculoviruses Expression Vector Baculoviruses General Features Baculoviruses Molecular...

Lessons from Successful Vaccines against Other Pathogens

Studies of the immune correlates of protection associated with existing vaccines reveal that Ab responses play a dominant role. Only BCG vaccination against Mycobacterium tuberculosis induces immunity in which Abs appear to have no role. Since CTL responses are likely to be required for an effective HIV-1 vaccine, traditional vaccine technologies are likely to be suboptimal, or counter-indicated due to safety concerns. Many existing vaccines are based on live-attenuated microorganisms. Such...

Manifestations of Antigenic Variation

Antigenic variation refers to the observation that different isolates of a single virus species may show variable cross-reactivity when tested with a standard serum. The homologous virus (the isolate that was used to raise the antiserum) usually shows the highest reactivity. Cross-reactivities with other viruses of the same species may vary from high to zero. While zero cross-reaction is due to a different type or subtype of the species, intermediate reactivities define antigenic groups or...

Opportunistic Infections and Malignancies Associated with HIV Infection

OIs and malignancies in patients with HIV infection emerge as a consequence of immune deficiency related to CD4+ T-lymphocyte depletion. A CD4+ T-lymphocyte count below 200 cells per mm3 is defined as AIDS even in the absence of other diseases or symptoms since this represents such an increase in risk for OI and malignancy. OIs and malignancies seen most commonly in HIV patients are listed in Table 1, and are discussed in detail in the 'AIDS surveillance case definition'. Although many of these...

Proteins Involved in Evading Host Defenses

A number of conserved ORFs encode proteins involved in evading host defense systems. The virus replicates in macrophages, which have important roles in activating and orchestrating the innate and adaptive immune responses. By interfering with macrophage function the virus can thus disrupt both of these types of host response. One protein, A238L, inhibits activation of the host transcription factor nuclear factor kappa B (NF-kB) and also inhibits calcineurin phosphatase activity....

Viral Subversion of Antigen Presentation

Considering the crucial role of antigen presentation for host defense, it is not surprising that many viruses have evolved maneuvers to evade or divert this process. Particularly, the essential role played by APCs in host defense to pathogens makes them an ideal target for viruses to suppress the immune response, thereby maximizing their chances of survival, replication, and transmission. Indeed, many viruses that cause major health problems are able to interfere with the ability of APCs to...

Particle Structure and Composition

Figure 1 shows an electron micrograph of AMV. The four major classes of particles in AMV preparations are called bottom component (B), middle component (M), top component b (Tb), and top component a (Ta). B, M, and Tb are bacilliform and contain the genomic RNAs 1,2, and 3, respectively. Ta contains two molecules of the subgenomic RNA 4 and can be subdivided into bacilliform Ta-b and spheroidal Ta-t particles. The bacilliform particles are all 19 nm wide and have lengths of 56 nm (B), 43 nm...

Diagnostic Techniques Plant Viruses

R Koenig and D-E Lesemann, Biologische Bundesanstalt f r Land- und Forstwirtschaft, Brunswick, Germany G Adam, Universit t Hamburg, Hamburg, Germany S Winter, Deutsche Sammlung fur Mikroorganismen und Zellkulturen, Brunswick, Germany 2008 Elsevier Ltd. All rights reserved. Diagnostic techniques for plant viruses are indispensable for at least three major sets of applications 1. the identification and classification of viruses associated with 'new' plant diseases (primary diagnosis) 2. the...

Gene Parities and Phylogeny

Gene parity plots, have shown that genes are basically organized in a collinear manner in closely related baculovirus genomes. Many viruses have distinct rearrangements such as deletions, inversions, insertions, etc. that are revealed when comparing two genomes. Data have shown that in comparisons of the NeleNPV genome with those from representatives group I NPVs (AcMNPV) and group II NPVs (HaSNPV), a GV (PxGV) and CuniNPV, the gene order was not generally conserved. Except for a central...

Conclusion About Virous Infection

The three examples of geminivirus emergence presented here provide examples of the importance of different factors that favor the emergence of gemini-viruses under very different conditions and environments. In the case of TYLCV, it is a relatively simple case with a single monopartite geminivirus that is transported, through human-based international trade, to various places in the world, and where this very effective virus overcomes existing local viruses and prevails. Although we do not know...

Prevention and Control of EBV Infection

The significant burden of EBV-associated tumors worldwide has prompted the development of novel therapeutic strategies that either specifically target viral proteins or exploit the presence of the virus in malignant cells. Pharmacological approaches include the use of agents to induce the expression EBV lytic cycle antigens, including virus-encoded kinases (EBV thymidine kinase and Figure 4 EBV gene expression in nasopharyngeal carcinoma (NPC). (a) shows a hematoxylin and eosin stain of a NPC...

Wheat Dwarf Virus

In continental areas of Europe and its borders, this virus may be very severe on winter wheat, durum wheat, triti-cale, rye, and barley. Two strains of wheat dwarf virus (WDV) have been characterized. Overall nucleic acid sequences of the wheat-adapted strain (WDV-W) which does not infect barley showed 16 divergence with the barley-adapted strain (WDV-B) which does not infect wheat. The monoclonal antibody MAB 3C10 developed in Germany detects only WDV-B. The two strains have several common...

Organization of the Dicistrovirus Genome

Rna Replication Comoviruses

The single-stranded genomes possess a 5' untranslated region (5' UTR) of 500-800 nt followed by two open reading frames (ORFs) of c. 5500 and 2600 nt. The ORFs are separated by an untranslated region of 190 nt, commonly referred to as the intergenic region (IGR) (Figure 4). Table 1 Members of the virus family Dicistroviridae. Isolate and vernacular names are shown in brackets. Accession number for whole genome sequences are also given. A recently suggested taxonomy that places ABPV, KBV,...

Recognition of Emerging and Reemerging Virus Diseases

The advent of highly specific molecular techniques such as the polymerase chain reaction (PCR) in the early 1980s permitted the detection and grouping of viruses on the basis of genome nucleotide sequence analysis, and in several respects these techniques have replaced sero-logical analyses for the characterization of viruses. Although it is still important to isolate viruses in cell culture for their complete characterization, it is now possible directly to detect viruses in diseased tissues...

Rice Grassy Stunt

Rice grassy stunt was first observed in 1963 in the Philippines, where the characteristic stunting was initially referred to as 'yellow dwarf' or 'rice rosette'. This disease is now present in China, India, Indonesia, Japan, Malaysia, Sri Lanka, Taiwan, and Thailand. The association of this disease with the brown planthopper, N. lugens, was made in 1964. The causal agent of rice grassy stunt was isolated in the early 1980s, as a member of a distinct species of the genus Tenuivirus. Hence, rice...

Phylogeny of Fish Retroviruses

Retroviruses have been classified into seven genera based largely on highly conserved amino acid sequences in the retroviral reverse transcriptase gene. While the majority of the viral sequences employed in this classification represent mammalian and avian retroviruses, a new genus termed Epsilonretroviruses, representing the fish retroviruses WDSV, WEHV-1, WEHV-2, has been added to the most recent classification. As more retroviral sequences from lower vertebrates have been identified, it has...

Coding Strategies of the Viral Genomes

Complete nucleotide sequences have been determined for at least one representative of each genus in the Bunyaviridae which has allowed the coding strategies of the individual genome segments to be elucidated. These are shown schematically in Figure 4. The L RNA encodes the L protein using a conventional negative-strand strategy, that is, in a complementary positivesense mRNA. The L protein contains motifs found in all RNA polymerases, and expression of recombinant L proteins, via a variety of...

Clinical Manifestations

Coxsackievirus infections can result in a wide variety of disease syndromes (Table 2). Most infections are asymptomatic or result in only mild upper respiratory tract symptoms (common cold). Other mild enteroviral illness, such as fever, headache, malaise, and mild gastrointestinal symptoms, may also occur. Serious illness that brings the patient to the attention of a physician is much less frequent. Inapparent infections and prolonged excretion of virus, especially in stools, are common. These...

Clinical Features of Infection

HSV-1 and HSV-2 exhibit similar clinical manifestations. They infect neonates, children, and adults, and produce a wide spectrum of diseases including mucous membrane and skin lesions, ocular, visceral, and CNS disease. The incubation period is 1-26 days (median 6-8 days). Age, gender, host genetic factors, immune competence, associated illnesses, and virulence of the infecting virus strain influence severity. Most (70-90 ) childhood HSV-1 infections are asymptomatic. In children 1-3 years of...

Pathology and Histopathology

In horses experimentally or fatally infected with EAV, the most common gross lesions are edema, congestion, and hemorrhage of subcutaneous tissues, lymph nodes, and viscera. Microscopic investigation of tissues from chronically infected horses, which had mildly swollen lymph nodes and slightly increased volumes of pleural and peritoneal fluids, revealed extensive lesions consisting of generalized endothelial damage to blood vessels of all sizes as well as severe glomerulonephritis. Both types...

Enterovirus 68 HEVD

Human enterovirus 68 (EV68) was originally isolated from four children with pneumonia and bronchiolitis in Table 1 Distribution of enterovirus (sero)types in the old and new taxonomic subclasses Classical subgroup of enteroviruses serotype) number Table 1 Distribution of enterovirus (sero)types in the old and new taxonomic subclasses Classical subgroup of enteroviruses serotype) number aNovel types identified by the VP1 coding sequence and registered by the Picornavirus Study Group of ICTV. PV,...

ChrysoP3 Shares a Phytoreo S7 Domain with Core Proteins of Phytoreoviruses

PcV dsRNA3 codes for its chryso-P3 protein, whereas Hv145SV, ACDACV, and CCRSACV dsRNA4s encode the corresponding chryso-P3s. Although the function of chryso-P3 is not known, sequence analysis and database searches offer some clues. ProDom database searches reveal that chryso-P3 sequences share a 'phytoreo S7 domain' with a family consisting of several phytoreo-virus P7 proteins known to be viral core proteins with nucleic acid binding activities. The consensus for the three chrysoviruses is...

The HIV1 Envelope Glycoprotein Variable Loops and Decoys

The target of HIV-neutralizing responses is the envelope glycoprotein. The glycoprotein complex exists in the virion membrane as a trimer of noncovalently associated hetero-dimers of surface protein (SU) and transmembrane protein (TM). The gp120 component is the most exposed component of the complex and contains five hypervariable loops (V1 V5) and five relatively invariant or constant regions (C1-C5). Vaccination with gp120 peptides, glycoprotein, or glycoprotein-expression constructs has met...

Replication

The receptor for EHV-1 entry has not been identified, but recent studies showed that the virus utilizes a unique entry receptor, as it efficiently entered and replicated in cells that lack the entry receptors HveA, HveB, and HveC used for entry by other alphaherpesviruses, such as HSV-1, HSV-2, and PRV. As with other alphaherpesviruses, EHV-1 entry is mediated by gD. The genes of the tissue culture-adapted KyA strain of EHV-1 are regulated at the transcriptional and transla-tional levels in a...

Genus Capillovirus

The genus Capillovirus contains three species Apple stem grooving virus (ASGV, the type species), Cherry virus A (CVA), and Lilac chlorotic leafspot virus (LiCLV) and a tentative species Nandina stem pitting virus (NSPV) (Table 1). Citrus tatter leaf virus (CTLV) from citrus and lily is indistinguishable from ASGV from Rosaceae fruit trees biologically, serologically, in genome organization, and in nucleotide sequence, and these days CTLV is regarded as an isolate of ASGV. ASGV occurs worldwide...

GV Specific Genes

Baculovirus genomes have been shown to contain a number of proteases. Those studied so far are classified as nonessential auxiliary genes. Enhancin is a metalloprotei-nase which digests the peritrophic membrane in the insect midgut to facilitate virus infection. It has so far been found in all Noctuidae-specific GVs and one Tortricidae-specific GV (choristoneura fumiferana GV) and also in several group II NPVs. A cysteine proteinase (cathepsin) is involved in postmortem degradation of the...

NPV Pathogenesis in Lepidopteran Larvae

Npv Virus Images

Occlusion dissolution in the gut lumen is a host range factor that begins a deadly race for the body of the caterpillar. Both virus and insect want to use the larval mass for the same ultimate purpose reproduction. However, virus and insect reproduction are mutually exclusive events hence, it is a life-or-death struggle. The larval protection strategy of covering most of its epithelium with cuticle gives a virus little opportunity for achieving contact with a living cell. The midgut is...

Pathogenesis and Immunity

Much of the disease associated with coxsackievirus infection is thought to be a direct result of tissue-specific cell destruction, analogous to the cytopathic effect in cultured cells (Figure 3). For the most part, the detailed mechanisms of virus-induced disease have not been well-characterized. The primary site of infection is typically the respiratory or gastrointestinal epithelium, leading to viremia that may result in a secondary site of tissue infection. Such secondary spread of virus to...

Rice Yellow Stunt

Rice yellow stunt (previously known as 'rice transitory yellowing') was first reported from southern Taiwan in 1960. The disease was initially believed to be caused by the lack of aeration in paddy fields. The characteristic foliar yellowing, stunting, and root rot were once blamed for the destruction of over 2000 ha of rice in the 1960s. In 1965, a virus was first suspected as the causal agent, and the leafhopper N. nigropictus (previously N. apicalis) was implicated as the vector. The name...

Genome Structure and Gene Expression

The genome is a single-stranded RNA (ssRNA), 7.4 9.1 kbp in size, which contains six open reading frames (ORFs), encoding the replicase, three putative protein components of movement proteins called triple gene block (TGB), the CP, and a putative nucleic acid-binding regulatory protein, from the 5' 3'-end in that order (Figure 2). In genome organization, the genus Carlavirus particularly resembles the genera Allexivirus, Foveavirus, Mandarivirus, and Potexvirus but is distinguished from them by...

Vaccines and Antiviral Drug Development

Because of the economic importance of CoV infection to livestock and domestic animals, a variety of live-attenuated and killed CoV vaccines have been tested in animals. Vaccines have been developed against IBV, TGEV, CCoV, and FIPV. However, these vaccines do not seem to provide complete protection from wild-type virus infection. In some cases, the wild-type CoV rapidly evolves to escape neutralization by vaccine-induced antibodies. In studies of vaccinated chickens, a live-attenuated IBV...

Classification of Cytomegaloviruses

Cytomegaloviruses (CMVs) are large, enveloped, double-stranded DNA viruses with an icosahedral capsid that belong to subfamily Betaherpesvirinae of the family Herpesviridae. There are three genera. Genus Cytomegalovirus contains human cytomegalovirus (HCMV species Human herpesvirus 5) and a number of other primate CMVs. Genus Muromegalovirus contains murine cytomegalovirus (MCMV Murid herpesvirus 1) and rat cytomegalovirus (RCMV Murid herpesvirus 2). Genus Roseolovirus contains human...

Contents

Adenoviruses General Features B Harrach 1 Adenoviruses Malignant Transformation and Oncology A S Turnell 9 Adenoviruses Molecular Biology K N Leppard 17 Adenoviruses Pathogenesis M Benko' 24 African Cassava Mosaic Disease J P Legg 30 African Horse Sickness Viruses P S Mellor and P P C Mertens 37 African Swine Fever Virus L K Dixon and D Chapman 43 AIDS Disease Manifestation A Rapose, J East, M Sova and W A O'Brien 51 AIDS Global Epidemiology P J Peters, P H Kilmarx and TD Mastro 58 AIDS Vaccine...

Mathematical Modeling

From the time of William Farr, who studied epidemic disease problems in the 1870s, mathematicians have been interested in 'epidemic curves' and secular trends in the incidence of infectious diseases. With the development of computer-based mathematical modeling techniques, there has been a resurgence of interest in the population dynamics of infectious diseases. There has also been a resurgence in controversies surrounding the use of models critics say 'for every model there is an equal and...

Vaccination

Vaccination is the main method of prophylaxis and Akabane vaccines have been produced in Japan and Australia. In Japan and Australia, inactivated vaccines have been developed that induce high antibody titers after two doses given with a 4 week interval. In trials, these vaccines prevented development of a viremia and fetal infection on challenge or after natural exposure and were safe when used in pregnant animals. As antibody titers decline fairly rapidly, annual revaccination is recommended....

Pathogenicity

There is considerable variation in the pathogenicity of strains of capripoxvirus. Little is known concerning the genes responsible in the capripoxvirus genome for virulence or host restriction some preliminary results have been published. Figure 1 Sheeppox showing rhinitis and conjunctivitis. a month in sheep and goats, whereas in cattle the necrotic papules that penetrate the thickness of the skin may remain as 'sitfasts' for up to a year. Severe disease is accompanied by significant loss of...

Pathogenesis

BTV produces a spectrum of conditions from subclinical infection to severe and fatal disease, depending on virus strain and host species. Virus is transmitted to vertebrate hosts through blood-feeding insect vectors and infectious particles migrate to lymph nodes where they initially replicate and subsequently spread to spleen, thymus, and other lymph nodes. In the final phase of infection, the virus begins circulating in the bloodstream and can persist for several months. In certain vertebrate...

Noncoding Regions and cisSignals

The first region of BMV RNAs to attract attention as a potential regulatory element was the 3'-end. Synergistic work by multiple groups showed that the 3'-noncoding regions of BMV RNAs are highly conserved, multifonc-tional domains that direct negative-strand RNA synthesis, contribute to RNA encapsidation, translation, and stability, and possess multiple tRNA-like features and functions. Limited early sequence data showed that BMV RNAs 1-4 share a tRNA-like CCAOH 3'-end. In 1972, Hall and...

Nodaviridae

Members of the Nodaviridae that infect fish belong to the genus Betanodavirus for which the type species is Striped jack nervous necrosis virus (SJNNV). These viruses are nonenveloped with icosahedral symmetry and virion diameters of approximately 30 nm. The viral genome consists of two molecules of positive-sense ssRNA. RNA1, the largest RNA genome segment encodes the viral polymerase. RNA2 encodes the virion capsid protein. A third RNA, transcribed from the 3' terminal region of RNA1, encodes...

Implications for Vaccine Development

Our increasing knowledge of the structure of viral epi-topes has given rise in some quarters to the expectation that it should be possible to develop peptide-based viral vaccines. However, the results so far have been disappointing. In spite of the hundreds of viral epitopes that have been identified by studying the antigenicity of pep-tide fragments of viral proteins, no commercial peptide vaccine has yet reached the marketplace. Although most peptide fragments are immunogenic in the sense...

Other Control Methods

Although ACMV and EACMV-like CMGs interact syn-ergistically, there is evidence that EACMV-like CMGs may hinder infection by other EACMV-like viruses and interfere with their replication. Studies in Uganda showed that plants initially infected by mild strains of EACMV-UG were much less likely to become severely diseased when exposed in the field than plants initially CMG-free. This cross-protective effect seems to be an important cause of symptom amelioration in post-CMD pandemic areas of East...

Electron Microscopy of Viruses

G Schoehn and R W H Ruigrok, CNRS, Grenoble, France 2008 Elsevier Ltd. All rights reserved. Most viruses are too small to be observed with light microscopy and many are too large or too irregular to crystallize. Therefore, electron microscopy (EM) is the method of choice for the direct visualization of viruses and viral proteins or subviral particles. However, electrons do not travel far in air and therefore the inside of the microscope has to be under very high vacuum (10 5 to 108 torr). This...

Host Range and Transmission

BCMV naturally infects P. vulgaris (kidney bean), P. acutifolius (tepary bean), P. atropurpureus, P. coccineus (runner bean), P. mungo (black gram), Glycine max (soybean), Macroptilium lathyroides (horse gram), Pisum sativum (pea), Rhynchosia minima, Vicia faba (broad bean), Vigna radiata (mung bean, green gram), V. angularis (azuki bean), and V. unguiculata (cowpea). Peanut stripe isolates naturally infect Arachis hypogea (peanut), Dolichos lablab (hyacinth bean), Indigofera amoena, G. max,...

Modes of Transmission

HIV can be transmitted by sexual contact, exposure to blood, and from mother to child with variable efficiency (Table 1). Although HIV has been isolated from a variety of body fluids, only blood, semen, genital fluids, and breast milk have been proven as sources of infection. Unprotected sexual contact is the predominant mode of HIV transmission throughout the world. Despite a relatively low efficiency of transmission per sexual act, numerous factors can enhance transmission. Receptive anal...