Multiple recombinant events in human T-cell Leukemia virus Type 1: complete sequences of recombinant African strains

Cassar, Olivier; Desrames, Alexandra; Marçais, Ambroise; Gout, Olivier; Taylor, Graham P.; Hermine, Olivier; Soriano, Vincent; Mendoza, Carmen de; Dehan, Océane; Mener, Margot Le; Afonso, Philippe V.; Gessain, Antoine

doi:10.1080/22221751.2020.1752117

Cited by 11 publications

(8 citation statements)

References 28 publications

(44 reference statements)

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“…Indeed, the junction corresponds to the first shift in RNA template of the reverse transcriptase. In Senegal and Ghana, we also identified another clade (a-G-rec) resulting from recombination between a-WA and a-Sen strains (132). In this clade, we identified two points of recombination, one at the U3/RU5 junction and the other in the env gene.…”

Section: Recombination Occurs In Htlv-1mentioning

confidence: 82%

“…We recently showed that the a-Sen clade arose from recombination between a-WA and a-NA strains (130). Furthermore, some strains present in Guinea and Ghana coalesce into a subgroup named a-G-rec, which also arose through recombination between a-WA and a-NA strains (see the next section for more details) (132). The size of the circles is proportional to the number of strains identified.…”

Section: Genetic Diversitymentioning

confidence: 99%

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Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area

et al. 2023

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The African continent is considered the largest high endemic area for the oncogenic retrovirus HTLV-1 with an estimated two to five million infected individuals. However, data on epidemiological aspects, in particular prevalence, risk factors and geographical distribution, are still very limited for many regions: on the one hand, few large-scale and representative studies have been performed and, on the other hand, many studies do not include confirmatory tests, resulting in indeterminate serological results, and a likely overestimation of HTLV-1 seroprevalence. For this review, we included the most robust studies published since 1984 on the prevalence of HTLV-1 and the two major diseases associated with this infection in people living in Africa and the Indian Ocean islands: adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-1-associated myelopathy (HAM/TSP). We also considered most of the book chapters and abstracts published at the 20 international conferences on HTLV and related viruses held since 1985, as well as the results of recent meta-analyses regarding the status of HTLV-1 in West and sub-Saharan Africa. Based on this bibliography, it appears that HTLV-1 distribution is very heterogeneous in Africa: The highest prevalences of HTLV-1 are reported in western, central and southern Africa, while eastern and northern Africa show lower prevalences. In highly endemic areas, the HTLV-1 prevalence in the adult population ranges from 0.3 to 3%, increases with age, and is highest among women. In rural areas of Gabon and the Democratic Republic of the Congo (DRC), HTLV-1 prevalence can reach up to 10-25% in elder women. HTLV-1-associated diseases in African patients have rarely been reported in situ on hospital wards, by local physicians. With the exception of the Republic of South Africa, DRC and Senegal, most reports on ATL and HAM/TSP in African patients have been published by European and American clinicians and involve immigrants or medical returnees to Europe (France and the UK) and the United States. There is clearly a huge underreporting of these diseases on the African continent. The genetic diversity of HTLV-1 is greatest in Africa, where six distinct genotypes (a, b, d, e, f, g) have been identified. The most frequent genotype in central Africa is genotype b. The other genotypes found in central Africa (d, e, f and g) are very rare. The vast majority of HTLV-1 strains from West and North Africa belong to genotype a, the so-called ‘Cosmopolitan’ genotype. These strains form five clades roughly reflecting the geographic origin of the infected individuals. We have recently shown that some of these clades are the result of recombination between a-WA and a-NA strains. Almost all sequences from southern Africa belong to Transcontinental a-genotype subgroup.

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Section: Recombination Occurs In Htlv-1mentioning

confidence: 82%

Section: Genetic Diversitymentioning

confidence: 99%

Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area

et al. 2023

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“…In addition, although recombinant forms of HTLV-1 have been described only in some African strains ( 47 ), we could not exclude recombinant forms of HTLV-1 as well HTLV-2 in coinfected individuals, as well as pseudotyping of HIV and HTLV-1/2.…”

Section: Discussionmentioning

confidence: 99%

Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals

Campos

Caterino–de–Araujo

2020

mSphere

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Provirus mutations of human T-lymphotropic virus 1 (HTLV-1), mostly the lack of the 5′ long terminal repeat (LTR) genomic region, have been described and associated with severe adult T cell leukemia/lymphoma (ATLL), non-sense point mutations with low proviral load, and Western blotting indeterminate results. Until now, no information concerning provirus mutations of HTLV-2 and its consequences, as well as those of HTLV-1/2 in HIV-coinfected individuals, had been described. Therefore, we searched for these mutations in provirus samples of 44 HIV/HTLV-1- and 25 HIV/HTLV-2-coinfected individuals. Using protocols well established for amplification and sequencing of segments of the LTR, env, and tax regions, we searched for defective type 1 particles that retain LTRs and lack internal sequences and type 2 particles that lack the 5′LTR region. In addition, using as references the prototypes ATK (HTLV-1) and Mo (HTLV-2), we searched for point mutations in the LTR and synonyms and nonsynonymous mutations and non-sense mutations in env and tax regions. Defective HTLV-1 and HTLV-2 provirus type 1 or 2 was detected in 31.8% of HIV/HTLV-1- and 32.0% of HIV/HTLV-2-coinfected individuals. Synonymous and nonsynonymous mutations were identified mostly in HTLV-2 and associated with lower levels of specific antibodies. No non-sense mutations that resulted in premature termination of Env and Tax proteins were detected. On the contrary, mutation in the stop codon of Tax2a produced a long protein characteristic of the HTLV-2c subtype. The clinical significance of these mutations in coinfected individuals remains to be defined, but they confirmed the lower sensitivity of serological and molecular diagnostic tests in HIV/HTLV-1/2 coinfections. IMPORTANCE HTLV-1 and HTLV-2 are endemic to Brazil, and they have different effects in HIV/AIDS disease progression. HIV/HTLV-1 has been described as accelerating the progression to AIDS and death, while HIV/HTLV-2 slows the progression to AIDS. Provirus mutations of HTLV-1 were implicated in severe leukemia development and in problems in the diagnosis of HTLV-1; in contrast, provirus mutations of HTLV-2 had not been confirmed and associated with problems in HTLV-2 diagnosis or disease outcome. Nevertheless, data obtained here allowed us to recognize and understand the false-negative results in serologic and molecular tests applied for HTLV-1 and HTLV-2 diagnosis. Defective proviruses, as well as synonymous and nonsynonymous mutations, were associated with the diagnosis deficiencies. Additionally, since HIV-1 and HTLV-1 infect the same cells (CD4 positive), the production of HIV-1 pseudotypes with HTLV-1 envelope glycoprotein during HIV/HTLV-1 coinfection cannot be excluded. Defective provirus of HTLV-2 and Tax2c is speculated to influence progression to AIDS.

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“…We also observed opposite effects of HTLV-1 expression on ICAM-1 and LFA-1 , which interact between infected and uninfected cells to promote virological synapse formation (50; 72). Despite recent reports of possible recombination events in the evolutionary history of some HTLV-1 strains (73; 74), the presence of a single integrated provirus in the majority of infected cells (31) suggests HTLV-1 has mechanisms to restrict superinfection (75). The downregulation of LFA-1 during reactivation might reduce the likelihood of superinfection following an encounter between infected cells, although LFA-1 is expressed in infected cells before reactivation at a higher level than in uninfected cells.…”

Section: Discussionmentioning

confidence: 99%

The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle

Aristodemou

Rueda

Taylor

et al. 2023

Preprint

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Infections by Human T cell Leukaemia Virus type 1 (HTLV-1) persist for the lifetime of the host by integrating into the genome of CD4+ T cells. Proviral gene expression is core to proviral survival and the maintenance of the proviral load, through the pro-proliferative changes it induces in infected cells. Despite their role in HTLV-1 infection and a persistent cytotoxic T lymphocyte response raised against them, proviral transcripts from the sense-strand are rarely detected in fresh cells extracted from the peripheral blood, and have recently been found to be expressed intermittently by a small subset of cells at a given time. Ex vivo culture of infected cells prompts synchronised proviral expression in infected cells from peripheral blood, allowing the study of factors involved in reactivation in primary cells. Here, we used bulk RNA-seq to examine the host transcriptome over six days in vitro, following proviral reactivation in primary peripheral CD4+ T cells isolated from subjects with non-malignant HTLV-1 infection. Infected cells displayed a conserved response to reactivation, characterised by discrete stages of gene expression, cell division and subsequently horizontal transmission of the virus. We observed widespread changes in Polycomb gene expression following reactivation, including an increase in PRC2 transcript levels and diverse changes in the expression of PRC1 components. We hypothesize that these transcriptional changes constitute a negative feedback loop that maintains proviral latency by re-deposition of H2AK119ub1 following the end of proviral expression. Using RNAi, we found that certain deubiquitinases, BAP1, USP14 and OTUD5 each promote proviral transcription. These data demonstrate the detailed trajectory of HTLV-1 proviral reactivation in primary HTLV-1-carrier lymphocytes and the impact on the host cell.

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Multiple recombinant events in human T-cell Leukemia virus Type 1: complete sequences of recombinant African strains

Cited by 11 publications

References 28 publications

Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area

Geographic distribution, clinical epidemiology and genetic diversity of the human oncogenic retrovirus HTLV-1 in Africa, the world’s largest endemic area

Provirus Mutations of Human T-Lymphotropic Virus 1 and 2 (HTLV-1 and HTLV-2) in HIV-1-Coinfected Individuals

The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle

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