Human T-Cell Lymphotropic Viruses

William M. Switzer; Walid Heneine; S. Michele Owen

doi:10.1128/9781555817381.ch83

Chapter 83 : Human T-Cell Lymphotropic Viruses

Authors: William M. Switzer, Walid Heneine, S. Michele Owen

Content Type: Reference

Publication Year: 2015

Category: Clinical Microbiology

Book DOI: 10.1128/9781555817381

Chapter DOI: 10.1128/9781555817381.ch83

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Abstract:

Human T-cell lymphotropic viruses (HTLVs) are complex retroviruses that consist of four major groups (HTLV-1, HTLV-2, HTLV-3, and HTLV-4) of which two (HTLV-1 and -2) have spread globally to infect millions of persons and are known to cause neurological and neoplastic diseases. Phylogenetic analysis with simian T-cell lymphotropic viruses (STLVs) show that HTLV-1, HTLV-2, and HTLV-3 all likely originated from multiple cross-species infections. A simian counterpart of HTLV-4 has recently been found in gorillas in Cameroon. Although an understanding of the epidemiology of HTLV-3 and -4 infection is limited by identification of small numbers of infected persons in Cameroon, HTLV-1 and -2 are transmitted sexually, vertically from mother to-child, and parenterally by blood transfusion and by sharing needles during intravenous drug use. Blood screening has limited the blood-borne transmission of HTLV-1 and -2, except in resource-limited countries like those in Africa where blood screening for these viruses is not done. HTLV testing is performed using standard serological and molecular tools. Disease has been associated mostly with only HTLV-1 infection and occurs in less than 5% of infected persons. Unlike other complex retroviruses, HTLVs encode proteins on the minus strand, called antisense proteins of HTLV (APH), that are believed to play a role in viral replication and disease. Much more research is needed to understand how HTLV causes disease, to determine the geographical distribution of HTLV-3 and -4, and to evaluate whether HTLV-3 and -4 can be transmitted from person to person and cause disease.

Citation: Switzer W, Heneine W, Owen S. 2015. Human T-Cell Lymphotropic Viruses, p 1458-1469. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch83

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Human T-Cell Lymphotropic Viruses

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FIGURE 1

Genomic organization of HTLV. LTR, long terminal repeat; Gag, group-specific antigen; env, envelope; pol, polymerase (including reverse transcriptase and integrase); pro, protease; rex, regulator of viral expression; tax, transcriptional activator; HBZ, HTLV-1 basic leucine zipper-like protein also known as the antisense protein of HTLV (APH). Miscellaneous accessory genes (not shown) are located in the pX region, located between the env gene and the 3′ LTR region of HTLV. The Gag and Env proteins are the most immunogenic, and antibodies to these proteins are commonly detected by serological tests (EIA and Western blotting). PCR assays are typically designed to detect regions within the LTR region and gag, pol, env, and/or tax genes. doi:10.1128/9781555817381.ch83.f1

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FIGURE 1

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FIGURE 2

Serologic testing algorithm for the detection and confirmation of HTLV-1 and -2 infections. If the initial screening immunoassay (EIA or ChLIA) is reactive, a repeat assay with the same specimen is performed in duplicate. If one or both of the repeat tests are reactive, the specimen is classified as repeatedly reactive and supplemental testing is done for confirmation. WB criteria shown are those used by the manufacturer and not the U.S. Public Health Service working group. In some cases, further follow-up is done using HTLV generic and/or type-specific PCR. *, HTLV-3 and -4 PCR is suggested if patient is linked to Cameroon or West Central Africa. r21e, recombinant p21 envelope (Env) protein; rgp46I and rgp46II, recombinant glycoprotein in Env specific for HTLV-1 or HTLV-2, respectively; Gag, group specific antigen; PBMC, peripheral blood mononuclear cells. doi:10.1128/9781555817381.ch83.f2

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FIGURE 2

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FIGURE 3

Western blot (WB) analysis of representative plasma or serum specimens from persons infected with (A) HTLV-1, (B) HTLV-2, (C) HTLV-1/2 untypeable, (D) indeterminate, and (E) HTLV-3 and HTLV-4. Representative seroreactivity patterns are shown for WBs from MP Biomedical (HTLV-2.4 version), which contain HTLV-1 antigens spiked with recombinant r21e (common to HTLV-1 and HTLV-2) and two external envelope recombinant proteins specific for HTLV-1 (rgp46I) and HTLV-2 (rgp46II). (A) Typical patterns for HTLV-1 reactivity (lanes 1 to 5), atypical reactivity lacking p24 Gag response (lane 6), and specimens with high antibody titers showing dual reactivity to both rgp46 proteins (lanes 7 and 8; titration of sera results in reactivity only to rgp46I). (B) Typical patterns for HTLV-2 reactivity (lanes 1 to 6; note that reactivity to the p24 band is stronger than to the p19 band, which is usually absent from sera from HTLV-2-infected persons). (C) HTLV-1/2-positive but untypeable specimens, with reactivity to Gag (p24, with or without p19) and r21e but not gp46I or gp46II. Lanes 1 and 2: characteristic patterns of specimens that are usually found to contain HTLV-1 after additional testing; lanes 3 to 5: characteristic patterns of specimens that are usually found to contain HTLV-2 after additional testing. (D) Typical patterns from HTLV indeterminate specimens. Shown are typical HTLV Gag indeterminate profiles frequently found in plasma or sera from individuals originating from tropical regions (Central Africa, Papua New Guinea, etc.) (lanes 1 to 4) and those from low-risk populations (lanes 5 to 7). In the great majority of cases, neither HTLV-1 nor HTLV-2 infection could be demonstrated in samples with such seroreactivity using PCR testing. (E) Seroreactivity observed in HTLV-3-infected (lane 4) and HTLV-4-infected (lane 5) persons from Cameroon. Plasma from an HTLV-3-infected person (Cam2026ND) was weakly reactive to p24, p19, r21e, and rgp46I. Plasma from the HTLV-4-infected person (Cam1863LE) was weakly reactive to p24, r21e, and rgp46II, but was strongly reactive to p19, similar to that seen in HTLV-1-infected specimens. Lanes 1 and 2 are from HTLV-1- and -2-infected persons, respectively, while lane 3 is reactivity of negative control plasma. doi:10.1128/9781555817381.ch83.f3

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FIGURE 3

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Tables

Human T-Cell Lymphotropic Viruses

/content/10.1128/9781555817381.mcm11.ch83.ch83.tab001

TABLE 1

Summary of serological and supplemental confirmatory tests for HTLV infection

TABLE 1

Summary of serological and supplemental confirmatory tests for HTLV infection