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Chapter 80 : Human T-Cell Lymphotropic Virus Types 1 and 2

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Abstract:

Human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2, respectively) are part of the family and members of the genus. However, high-risk populations, such as intravenous drug users (IDUs), in which HTLV-2 infection predominates over HTLV-1 infection, are reported to have a seroprevalence of up to 20%. IDU and sex with IDUs are the most important risk factors for HTLV-2 transmission. Peripheral blood mononuclear cells (PBMCs) are appropriate specimens for nucleic acid detection and virus isolation since HTLV-1 and HTLV-2 are cell-associated viruses. Two qualitative PCR procedures, utilizing primers in the or gene region, have been used to confirm and differentiate between HTLV-1 and HTLV-2 infections. The first uses HTLV consensus primers that allow amplification of both viruses; typing is achieved either by hybridizing the product to an HTLV-1-specific or HTLV-2-specific probe or by specific restriction digestion pattern analysis. The second approach employs type-specific primers and probes in separate amplifications. Testing for antibodies to HTLV-1 and HTLV-2 should be performed for all blood donors and any patients presenting with relevant clinical signs and symptoms. A typical algorithm for HTLV testing for diagnostic purposes is outlined in this chapter. If the initial screening immunoassay (EIA or ChLIA) is reactive, a repeat assay of the same specimen is performed in duplicate.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80

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Figures

Image of FIGURE 1
FIGURE 1

Organization of the HTLV-1 (9,046 bp) and -2 (8,952 bp) proviral genomes. MA, matrix; CA, capsid; NC, nucleocapsid; SU, surface; TM, transmembrane; RT, reverse transcriptase; PR, protease. The gag and env proteins are most immunogenic, and antibodies to these proteins are commonly detected by serological tests (EIA and WB). PCRs are designed to detect regions within the LTR region and the , , , and/or gene.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80
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Image of FIGURE 2
FIGURE 2

Unrooted phylogenetic tree generated by the neighbor-joining method using a fragment of the LTR region (622 bp) of representative sequences of the different subtypes of HTLV-1 and HTLV-2 strains. Bootstrap support (1,000 replicates) is noted on the branches of the tree. The branch lengths are drawn to scale, with the bar indicating 0.1 nucleotide replacement per site. The four main HTLV-1 subtypes (a, b, c, and d), as well as the three main subtypes of HTLV-2 (a, b, and d), are represented. HTLV-1e and HTLV-1f represent the two other rare HTLV-1 subtypes, which have so far been found in a few inhabitants of Central Africa.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80
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Image of FIGURE 3
FIGURE 3

Serologic testing algorithm for the detection and confirmation of HTLV-1 and -2 infection. 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 the purpose of confirmation. WB criteria shown are those used by the manufacturer and not the PHS working group. In some cases, further follow-up is done using PCR.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80
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Image of FIGURE 4
FIGURE 4

Western blot analysis of representative plasma or serum specimens from persons infected with HTLV-1 (A), HTLV-2 (B), and untypeable HTLV-1/2 (C). Representative seroreactivity patterns are shown for WBs from MP Biomedicals (previously Genelabs Diagnostics; HTLV-2.4 version), which contain HTLV-1 antigens spiked with r21e (common to HTLV-1 and HTLV-2) and two external recombinant envelope proteins specific for HTLV-1 (rgp46) and HTLV-2 (rgp46). (A) Typical patterns for HTLV-1 reactivity (lanes 1 to 5), atypical reactivity lacking a p24 response (lane 6), and specimens with high antibody titers showing reactivity to both rgp46 proteins (lanes 7 and 8) (titration of sera results in reactivity only to rgp46). (B) Typical patterns for HTLV-2 reactivity (lanes 1 to 6) (note that the p24 band is stronger than p19 reactivity, which is usually absent from HTLV-2-infected sera). (C) HTLV-1/2-positive but untypeable specimens, with reactivity to gag (p24, with or without p19) and r21e but not gp46 or gp46. 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 and Papua New Guinea, etc.) (lanes 1 to 4) and those from low-risk populations (lanes 5 to 7). In the great majority of the cases, neither HTLV-1 nor HTLV-2 infection could be demonstrated in samples with such seroreactivity.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80
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Tables

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TABLE 1

Summary of serologic and supplemental confirmatory tests for HTLV-1 and HTLV-2 infections

FDA licensed, may be used for blood donor screening and as an aid in clinical diagnosis of HTLV-1 or HTLV-2 infection and related diseases. CE, Conformité Européenne.

Citation: Owen S, Gessain A, Dezzutti C, Cowan E, Lal R. 2011. Human T-Cell Lymphotropic Virus Types 1 and 2, p 1323-1332. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch80

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