Human T-Cell Lymphotropic Viruses

Corliss L. Newman; Joseph D. Rosenblatt

doi:10.1128/9781555818289.ch11

Chapter 11 : Human T-Cell Lymphotropic Viruses

Authors: Corliss L. Newman, Joseph D. Rosenblatt

Content Type: Monograph

Publication Year: 1998

Category: Microbial Genetics and Molecular Biology; Viruses and Viral Pathogenesis

Book DOI: 10.1128/9781555818289

Chapter DOI: 10.1128/9781555818289.ch11

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Abstract:

This chapter reviews the epidemiology, disease associations, molecular biology, and pathogenic mechanisms of human T-cell lymphotropic virus (HTLV) types I and II. Association of HTLV-I with two distinct disease processes, a malignancy and a chronic neurologic disorder, spurred worldwide surveys for prevalence of HTLV-I and associated diseases. Transmission of HTLV-I seems to require prolonged, close contact between individuals. Transfer of infected T cells is likely required. The three major reported routes of HTLV-I transmission include sexual intercourse, blood product transmission, and mother-to-child transfer. The most commonly used screening test for HTLV-I/HTLV-II is an enzyme-linked immunosorbent assay (ELISA) which uses a viral lysate-based antigen derived from HTLV-I infection of human T cells. Unlike human immunodeficiency virus (HIV), which has significant genetic differences between isolates, the various HTLV-I strains show a high degree of genetic conservation. There are two major hypotheses for pathogenesis in HTLV-I associated myelopathy (HAM)/tropical spastic paresis (TSP). The first hypothesis is that HTLV-I infects glial cells in the CNS and subsequently induces a cytotoxic immune response against these cells, leading to demyelination. The second hypothesis is that HTLV-I infection activates autoreactive T cells which then cause autoimmune destruction within the CNS (and perhaps in other areas). The molecular biology of HTLV-II is strikingly similar to that of HTLV-I. HTLV-I infection, however, has been linked to several disorders, especially adult T-cell leukemia/lymphoma (ATL) and HAM/TSP. HTLV-I and HTLVII have a similar genetic organization and regulation and share several unique transregulatory proteins.

Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

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Human T-Cell Lymphotropic Viruses

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Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

/content/10.1128/9781555818289.chap11.fig11-1

Figure 1

Skin involvement in a Japanese patient with ATL (courtesy of Masao Tomanaga).

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Figure 1

Skin involvement in a Japanese patient with ATL (courtesy of Masao Tomanaga).

Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

/content/10.1128/9781555818289.chap11.fig11-2

Figure 2

Typical lymphocytes with convoluted nuclei seen in ATL; also called “flower cells.”

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Figure 2

Typical lymphocytes with convoluted nuclei seen in ATL; also called “flower cells.”

Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

/content/10.1128/9781555818289.chap11.fig11-3

Figure 3

Molecular features of HTLV. (A) Genomic organization. LTRs and ORFs are depicted. Translational start (ATG) and stop (diamonds) codons are indicated. (B) HTLV produces multiple RNA species by splicing. ORFs encoded by the different RNA species are indicated. Solid lines represent exons and discontinuous lines represent introns. UP, unspliced; SP, singly spliced; DP, doubly spliced. (C) Translation of polycistronic messages by ribosomal framesMfting (FS). (D) Translation of polycistronic messages by readthrough of a weak translational ATG. (Used with permission from reference 27 .)

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Figure 3

Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

/content/10.1128/9781555818289.chap11.fig11-4

Figure 4

Model of Tax recruitment of the coactivator CBP to the HTLV-I promoter. For simplicity, only one of the three 21-bp repeats is shown. Tax in association with CREB and the viral CRE creates a high-affinity binding site that anchors CBP to the viral promoter. Once bound, CBP activates HTLV-I transcription through chromatin remodeling and recruitment of the general transcription machinery. TFIIB, transcription factor IIB; P/CAF, p300/CBP-associated factor; RNAP II, RNA polymerase II. (Used with permission from reference 42 .)

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Figure 4

Citation: Newman C, Rosenblatt J. 1998. Human T-Cell Lymphotropic Viruses, p 331-357. In McCance D (ed), Human Tumor Viruses. ASM Press, Washington, DC. doi: 10.1128/9781555818289.ch11

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