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Chapter 269 Human T-Lymphotropic Viruses (1 and 2)
Hal B. Jenson
Human T-lymphotropic viruses 1 (HTLV-1) and 2 (HTLV-2) are members of the Deltaretrovirus genus of the Retroviridae family, which are single-stranded RNA viruses that encode reverse transcriptase, an RNA-dependent DNA polymerase that transcribes the single-stranded viral RNA into a double-stranded DNA copy. HTLV-1 and -2 share approximately 65% genome homology and infect T cells, B cells, and synovial cells via the ubiquitous glucose transporter type 1 (GLUT1), which serves as the virus receptor. Circular viral DNA is transported into the nucleus where it is integrated into chromosomal DNA (provirus), evading the typical mechanisms of immune surveillance and resulting in lifelong infection. The host response is mediated by cytotoxic T lymphocytes resulting in lysis of infected cells. An exuberant inflammatory response with overproduction of cytokines contributes to developing nonmalignant disease. In addition, HTLV-1 was the first human retrovirus to be associated with cancer, as the cause of adult T-cell leukemia/lymphoma (ATL).
HTLV-1 infects 10-20 million persons globally. It is endemic in southwestern Japan (where >10% of adults are seropositive), areas of the Caribbean including Jamaica and Trinidad (up to 6%), and in parts of sub-Saharan Africa (up to 5%). Lower seroprevalence rates are found in South America (up to 2%) and Taiwan (0.1-1%). There is microclustering with marked variability within geographic regions.
The seroprevalence of HTLV-1 and HTLV-2 in the USA in the general population is 0.01-0.03% for each virus, with higher rates with increasing age. HTLV-1 infection correlates greatest with birth in endemic areas or sexual contact with persons from endemic areas. HTLV-2 infection correlates with intravenous illicit drug use. A prevalence of approximately 18% was found in a study of illicit drug users in the USA, often with concomitant HIV infection.
HTLV-1 and HTLV-2 are transmitted as cell-associated viruses by vertical transmission from mother to child and horizontal transmission through genital secretions, contaminated blood products, and intravenous illicit drug use. Vertical HTLV-1 transmission occurs primarily via breast-feeding from infected mothers, with a 3-fold increased risk of transmission with breast-feeding for >6 mo. Intrauterine and intrapartum transmission account for <5% of vertical transmission. In Japan, approximately 20-25% of children born to infected mothers become infected, and >90% of HTLV-1-infected children have HTLV-1-infected mothers. HTLV-2 may also be transmitted via breast-feeding but has a slightly lower reported transmission rate via breast milk of approximately 14%.
HTLV-1 and HTLV-2 infections are diagnosed by screening using 2nd generation enzyme immunoassay with confirmation by immunoblot, indirect immunofluorescence, or line immunoassays. Polymerase chain reaction can also be used to distinguish HTLV-1 from HTLV-2 infection.
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