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Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes

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Afonso, Philippe V., Cassar, Olivier, Gessain, Antoine·2019·Retrovirology
DOI 10.1186/s12977-019-0504-zPMC PMC6916231
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Abstract

Human T cell leukemia virus (HTLV-1) is an oncoretrovirus that infects at least 10 million people worldwide. HTLV-1 exhibits a remarkable genetic stability, however, viral strains have been classified in several genotypes and subgroups, which often mirror the geographic origin of the viral strain. The Cosmopolitan genotype HTLV-1a, can be subdivided into geographically related subgroups, e.g. Transcontinental (a-TC), Japanese (a-Jpn), West-African (a-WA), North-African (a-NA), and Senegalese (a-Sen). Within each subgroup, the genetic diversity is low. Genotype HTLV-1b is found in Central Africa; it is the major genotype in Gabon, Cameroon and Democratic Republic of Congo. While strains from the HTLV-1d genotype represent only a few percent of the strains present in Central African countries, genotypes -e, -f, and -g have been only reported sporadically in particular in Cameroon Gabon, and Central African Republic. HTLV-1c genotype, which is found exclusively in Australo-Melanesia, is the most divergent genotype. This reflects an ancient speciation, with a long period of isolation of the infected populations in the different islands of this region (Australia, Papua New Guinea, Solomon Islands and Vanuatu archipelago). Until now, no viral genotype or subgroup is associated with a specific HTLV-1-associated disease. HTLV-1 originates from a simian reservoir (STLV-1); it derives from interspecies zoonotic transmission from non-human primates to humans (ancient or recent). In this review, we describe the genetic diversity of HTLV-1, and analyze the molecular mechanisms that are at play in HTLV-1 evolution. Similar to other retroviruses, HTLV-1 evolves either through accumulation of point mutations or recombination. Molecular studies point to a fairly low evolution rate of HTLV-1 (between 5.6E−7 and 1.5E−6 substitutions/site/year), supposedly because the virus persists within the host via clonal expansion (instead of new infectious cycles that use reverse transcriptase).

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Fig. 1 Geographical distribution of the seven main molecular genotypes of HTLV-1 (a–g) and major pathways for the spread of the virus through the movements of infected populations
Fig. 1 Geographical distribution of the seven main molecular genotypes of HTLV-1 (a–g) and major pathways for the spread of the virus through the movements of infected populationsCC BY · PubMed Central
Fig. 2 Map of Africa showing the general distribution of HTLV-1 genotypes across the continent. The proportion of the different HTLV-1 genotypes and subgroups is presented for each African country. This figure incorporates the information from papers of molecular epidemiology available on PubMed [20, 21, 23–27, 30, 41, 44–46, 55, 68, 135–144]. It also incorporates results from two manuscripts in preparation (Cassar et al. and Filippone et al.), notably concerning the situation in Benin, Sierra Leone, Western Sahara, and Madagascar, where no data were available to our knowledge. Countries without indications have no informative published data on HTLV-1 genotypes between 1994 and 2019. The size of the circles is proportional to the number of strains identified. The smallest size corresponds to 1 characterized strain, the intermediate sizes to a maximum of 5 or 29 strains and the largest to a minimum of 30 strains. HTLV-1a-North African (HTLV-1 a-NA), HTLV-1a-Senegalese (HTLV-1 a-Sen), HTLV-1a-West African (HTLV-1 a-WA), HTLV-1b and HTLV-1a-Transcontinental (HTLV-1 a-TC) are the most common throughout the continent in North, West, Central and the Austral parts respectively. HTLV-1 d, -e, -f and-g have been identified in Central Africa (Cameroon, Central African Republic, and Gabon)
Fig. 2 Map of Africa showing the general distribution of HTLV-1 genotypes across the continent. The proportion of the different HTLV-1 genotypes and subgroups is presented for each African country. This figure incorporates the information from papers of molecular epidemiology available on PubMed [20, 21, 23–27, 30, 41, 44–46, 55, 68, 135–144]. It also incorporates results from two manuscripts in preparation (Cassar et al. and Filippone et al.), notably concerning the situation in Benin, Sierra Leone, Western Sahara, and Madagascar, where no data were available to our knowledge. Countries without indications have no informative published data on HTLV-1 genotypes between 1994 and 2019. The size of the circles is proportional to the number of strains identified. The smallest size corresponds to 1 characterized strain, the intermediate sizes to a maximum of 5 or 29 strains and the largest to a minimum of 30 strains. HTLV-1a-North African (HTLV-1 a-NA), HTLV-1a-Senegalese (HTLV-1 a-Sen), HTLV-1a-West African (HTLV-1 a-WA), HTLV-1b and HTLV-1a-Transcontinental (HTLV-1 a-TC) are the most common throughout the continent in North, West, Central and the Austral parts respectively. HTLV-1 d, -e, -f and-g have been identified in Central Africa (Cameroon, Central African Republic, and Gabon)CC BY · PubMed Central
Fig. 3 Phylogenetic representation of the HTLV-1 genotypes and subgroups. An alignment of complete LTR sequences (774-nt long) from 178 HTLV-1 strains was obtained. The unrooted phylogenetic tree was generated with the neighbor-joining method using the GTR model (gamma = 0.4953). Branch lengths are drawn to scale, with the bar indicating 0.01 nucleotide replacement per site. Numbers on each node indicate the percentage of bootstrap samples (of 1000 replicates). HTLV-1 genotypes (a–g) and subgroups (within HTLV-1a and HTLV-1c) are presented. References strains (presented in the table) are indicated in the tree, except Mel1 and Ethio10 for which the complete LTR sequence is not available
Fig. 3 Phylogenetic representation of the HTLV-1 genotypes and subgroups. An alignment of complete LTR sequences (774-nt long) from 178 HTLV-1 strains was obtained. The unrooted phylogenetic tree was generated with the neighbor-joining method using the GTR model (gamma = 0.4953). Branch lengths are drawn to scale, with the bar indicating 0.01 nucleotide replacement per site. Numbers on each node indicate the percentage of bootstrap samples (of 1000 replicates). HTLV-1 genotypes (a–g) and subgroups (within HTLV-1a and HTLV-1c) are presented. References strains (presented in the table) are indicated in the tree, except Mel1 and Ethio10 for which the complete LTR sequence is not availableCC BY · PubMed Central
Fig. 4 Diverse clusters can be identified within the HTLV-1a-TC subgroup. An alignment of LTR sequences (519-nt long) from 91 HTLV-1a-TC strains was obtained. Sequences from HTLV-1a-Jpn were used as outgroup. The phylogenetic tree was generated with the neighbor-joining method using the GTR model (gamma = 0.4953). Horizontal branch lengths are drawn to scale, with the bar indicating 0.01 nucleotide replacement per site. Values correspond to the approximate likelihood-ratio test for each clade
Fig. 4 Diverse clusters can be identified within the HTLV-1a-TC subgroup. An alignment of LTR sequences (519-nt long) from 91 HTLV-1a-TC strains was obtained. Sequences from HTLV-1a-Jpn were used as outgroup. The phylogenetic tree was generated with the neighbor-joining method using the GTR model (gamma = 0.4953). Horizontal branch lengths are drawn to scale, with the bar indicating 0.01 nucleotide replacement per site. Values correspond to the approximate likelihood-ratio test for each cladeCC BY · PubMed Central

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  • Current State of Therapeutics for HTLV-1

    Wang, T. T., Hirons, A., Doerflinger, M., Morris, K. V., Ledger, S., Purcell, D. F. J., Kelleher, A. D., & Ahlenstiel, C. L. (2024) · Viruses · doi:10.3390/v16101616 · Cited by 22

    “A caveat, however, is that immunocompetent HTLV-1 carrier mouse models demonstrate very little in vivo spread of infection with no evidence of disease, except for one report of tumorigenesis [125,126].”
    Background

See all 90

Metadata

Authors
Afonso, P. V., Cassar, O., & Gessain, A.
Affiliations
Institut Pasteur (FR)
Corresponding author
Afonso, Philippe V.
ORCID
Venue
Retrovirology
Publisher
Springer Science and Business Media LLC
Published
2019-12
Volume
16
Issue
1
Pages
39-39
ISSN
1742-4690 (ISSN-L)
DOI
10.1186/s12977-019-0504-z
PMC
PMC6916231
OpenAlex
W2995144025
Cited by
90
References
2
Citations by year
2026: 12 · 2025: 12 · 2024: 15 · 2023: 12 · 2022: 18 · 2021: 12 · 2020: 9
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Retrovirology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
Funders
labex IBEID (ANR10-LBX-62 IBEID)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
  • Health Sciences › Medicine › Hepatology › Hepatitis Viruses Studies and Epidemiology
Keywords
HTLV-1, human T-cell leukemia virus, viral genotypes, genetic diversity, molecular epidemiology, viral evolution, recombination, point mutations, evolutionary rates, clonal expansion, zoonotic transmission
MeSH terms
Africa, Animals, Genotype, Humans, Mutation, Phylogeny, Primates, RNA, Viral, Genetic Variation, Simian T-lymphotropic virus 1, Human T-lymphotropic virus 1, HTLV-I Infections, Molecular Epidemiology, Evolution, Molecular

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CoChat. (2026). Citation check: Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes. https://app.cochat.ai/papers/10.1186/s12977-019-0504-z
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Afonso, P. V., Cassar, O., & Gessain, A. (2019). Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes. Retrovirology. https://doi.org/10.1186/s12977-019-0504-z