Molecular epidemiological studies have shown that HTLV-2a is the predominant infection in IVDAs in urban North America. HTLV-2b seems to be the predominant subtype in Indian groups in Panama, Colombia and Argentina. Recently, it has been suggested the existence of a third molecular subtype of HTLV-2 - HTLV-2c - in urban Brazilian and Indian populations. HTLV-2c has LTR and env nucleotide sequences more closely related to HTLV-2a, but a nucleotide and a predicted amino acid sequence for tax similar to that of HTLV-2b.

A second well-characterized isolate of HTLV-2 (HTLV-2b) was obtained from an elderly Caucasian male with HCL whose illness was marked by splenomegaly, inaspirable bone marrow and the presence of circulating tartrate-resistant acid phos-phatase-positive (TRAP+) lymphoid cells with hairy cell morphology. The peripheral blood in this patient also contained a large number of atypical lymphoid cells that were TRAP-negative and of T cell origin. The patient's illness was observed over a 2-year period, and he was ultimately found to have two coexisting lymphoproliferative disorders of distinct T and B cell origin. Using cell-fractionation techniques, it was determined that oligoclonally integrated HTLV-2 DNA was detected in a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells of the affected patient. It was concluded that the patient harbored a TRAP+ B cell malignancy without integrated HTLV-2, and a CD8+ T cell lymphoproliferative syndrome containing oligoclonally inte grated HTLV-2, which had arisen from a single virally infected precursor cell, similar to what is observed for HTLV-1 and adult T all leukemia (ATL). This case still represents the most convincing evidence for potential involvement of HTLV-2 in a human malignancy. Other anecdotal cases of T cell malignancy in the setting of HTLV-2 infection, including a case of T cell prolymphocytic leukemia, have been documented. Nevertheless, an etiologic role for HTLV-2 in leukemia/lymphoma remains to be established.

HTLV-2 has also been observed in only two cases of a progressive spastic myelopathy in patients co-infected with HIV-1. Additional cases of myelopathy among HTLV-2-infected New Mexican Indians and African Americans in the US have also been reported. It would therefore appear that like HTLV-1, infection with HTLV-2 might predispose to a spastic myelopathy affecting sphincter control and motor function in the lower extremities. In several patients with neurologic syndromes related to HTLV-2, severe cerebellar dysfunction leading to ataxia was also noted. In a study of HTLV-2-infected IVDA, most carriers were noted to be asymptomatic and have normal absolute lymphocyte counts and immunologic T and B lymphocytic subsets. A modestly elevated absolute lymphocyte count was noted in 4 of 21 HTLV-2-infected IVDA, and several patients had a CD8+ T cell lymphocytosis, as well as an overall increase in the percentage of CD8+ HLA-DR-positive lymphocytes. No overt pathology was demonstrated in this cohort, although several IVDA were also noted to have moderate elevations in serum creatine phosphokinase levels, suggesting possible myositis. This finding was intriguing in view of reports of polymyositis found in association with HTLV-1 infection. Thus, most HTLV-2-infected IVDA have been asymptomatic, and have had no overt hematologic, neurologic or immunologic abnormalities other than occasional lymphocytosis.

Infectious dermatitis has been described in children infected with HTLV-1 and similar cases of prolonged dermatitis and frequent staphylococcal skin infections have been described in IVDA found to harbor HTLV-2. Whether this represents a prototypic illness associated with the virus is unknown. Epidemiologic studies of small populations of New Mexican Indians, identified as an HTLV-2-infected endemic population, have not disclosed an increase in T cell malignancies, B cell chronic lymphocytic leukemia or HCL. Thus, a conclusive link between HTLV-2 and a specific malignant or neurological disease has not yet been established.

Recent studies have shown that HTLV-2-infected individuals had an increased risk of pneumonia, minor fungal infection, abscess and lymphadenopathy and bladder or kidney infections. This new finding of increased prevalence of a variety of infections in HTLV-2-positive donors suggests immunologic impairment. However, whether HTLV-2 has an etiological role in predisposing infected individuals to such infections will require further investigation.

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