Identification and Molecular Characterization of New Simian T Cell Lymphotropic Viruses in Nonhuman Primates Bushmeat from the Democratic Republic of Congo

Ahuka‐Mundeke, Steve; Mbala-Kingebeni, Placide; Liégeois, Florian; Ayouba, Ahidjo; Lunguya-Metila, Octavie; Demba, Didace; Bilulu, Guy; Mbenzo-Abokome, Valentin; Inogwabini, Bila‐Isia; Muyembe‐Tamfum, Jean‐Jacques; Delaporte, Eric; Peeters, Martine

doi:10.1089/aid.2011.0211

Cited by 22 publications

(39 citation statements)

References 24 publications

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“…tax PCR positive samples were further characterized in 5'-LTR (386-689 bp) by amplifying a 450bp fragment with specific primers for the corresponding PTLV types as deduced from phylogenetic analyses of tax-PCR derived sequences. To that end, we used in the first round ENH280/PTLV1LTR5R1 and in the second round, Tatabox/5PLTR (Ahuka-Mundeke et al 2012, Mahieux et al 1997; Meertens et al 2001). PCR products were directly sequenced using an automated sequencer as described above.…”

Section: Methodsmentioning

confidence: 99%

“…Given the importance of bushmeat in daily subsistence it is thus important to extend studies on pathogens at the human/animal interface. Our previous studies in NHP bushmeat were conducted in 3 sites in West-Central DRC and showed an overall SIV and STLV prevalence of almost 20% and 8% respectively, in NHP bushmeat (Ahuka-Mundeke et al 2011; Ahuka-Mundeke et al 2012). Here we study simian retroviruses in NHP bushmeat mainly in Northern and Eastern DRC.…”

Section: Introductionmentioning

confidence: 98%

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High Prevalences and a Wide Genetic Diversity of Simian Retroviruses in Non-human Primate Bushmeat in Rural Areas of the Democratic Republic of Congo

et al. 2017

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Like the majority of emerging infectious diseases, HIV and HTLV are of zoonotic origin. Here we assess the risk of cross-species transmissions of their simian counterparts, SIV and STLV, from nonhuman primates (NHP) to humans in the Democratic Republic of Congo (DRC). A total of 331 samples, derived from NHP bushmeat, were collected as dried blood spots (DBS, n=283) or as tissue samples (n=36) at remote forest sites in northern and eastern DRC. SIV antibody prevalences in DBS were estimated with a novel high throughput immune assay with antigens representing the actual known diversity of HIV/SIV lineages. Antibody positive samples were confirmed by PCR and sequence analysis. Screening for STLV infection was done with universal primers in tax and new strains were further characterized in LTR. SIV and STLV infection in tissue samples was done by PCR only. Overall, 5% and 15.4% of NHP bushmeat was infected with SIV and STLV respectively. A new SIV lineage was identified in Allen's swamp monkeys (Allenopithecus nigroviridis). Three new STLV-1 subtypes were identified in Allen's swamp monkeys (Allenopithecus nigroviridis), blue monkeys (Cercopithecus mitis), red tailed guenons (Cercopithecus ascanius schmidti) and agile mangabeys (Cercocebus agilis). SIV and STLV prevalences varied according to species and geographic region. Our study illustrates clearly, even on a small sample size from a limited number of geograhic areas, that our knowledge on the genetic diversity and geographic distribution of simian retroviruses is still limited and that humans continue to be exposed to relative high proportions on infected NHP bushmeat.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

High Prevalences and a Wide Genetic Diversity of Simian Retroviruses in Non-human Primate Bushmeat in Rural Areas of the Democratic Republic of Congo

et al. 2017

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“…5]), there is no major riverine barrier that could prevent gene flow between those sites. (19,20), from which simian sequences closely related to sequences generated in this study stem.…”

Section: Discussionmentioning

confidence: 80%

“…This may suggest that the risk of acquiring STLV-1 from NHP is lower in DRC (despite high average contact rates) and that most transmission events result from human-to-human contacts. Notably, all newly generated Congolese NHP sequences belong to the "new subtype DRC" (19,20). This subtype forms a well-supported, thus far exclusively simian clade (bootstrap, 98 to 100; posterior probabilities, 1 [ Fig.…”

Section: Discussionmentioning

confidence: 99%

Bushmeat Hunting and Zoonotic Transmission of Simian T-Lymphotropic Virus 1 in Tropical West and Central Africa

Mossoun

Calvignac‐Spencer

Anoh

et al. 2017

J Virol

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Simian T-lymphotropic virus 1 (STLV-1) enters human populations through contact with nonhuman primate (NHP) bushmeat. We tested whether differences in the extent of contact with STLV-1-infected NHP bushmeat foster regional differences in prevalence of human T-lymphotropic virus 1 (HTLV-1). Using serological and PCR assays, we screened humans and NHPs at two Sub-Saharan African sites where subsistence hunting was expected to be less (Taï region, Côte d'Ivoire [CIV]) or more (Bandundu region, Democratic Republic of the Congo [DRC]) developed. Only 0.7% of human participants were infected with HTLV-1 in CIV (n ϭ 574), and 1.3% of humans were infected in DRC (n ϭ 302). Two of the Ivorian human virus sequences were closely related to simian counterparts, indicating ongoing zoonotic transmission. Multivariate analysis of human demographic parameters and behavior confirmed that participants from CIV were less often exposed to NHPs than participants from DRC through direct contact, e.g., butchering. At the same time, numbers of STLV-1-infected NHPs were higher in CIV (39%; n ϭ 111) than in DRC (23%; n ϭ 39). We conclude that similar ultimate risks of zoonotic STLV-1 transmission-defined as the product of prevalence in local NHP and human rates of contact to fresh NHP carcasses-contribute to the observed comparable rates of HTLV-1 infection in humans in CIV and DRC. We found that young adult men and mature women are most likely exposed to NHPs at both sites. In view of the continued difficulties in controlling zoonotic disease outbreaks, the identification of such groups at high risk of NHP exposure may guide future prevention efforts.IMPORTANCE Multiple studies report a high risk for zoonotic transmission of bloodborne pathogens like retroviruses through contact with NHPs, and this risk seems to be particularly high in tropical Africa. Here, we reveal high levels of exposure to NHP bushmeat in two regions of Western and Central tropical Africa. We provide evidence for continued zoonotic origin of HTLV-1 in humans at CIV, and we found that young men and mature women represent risk groups for zoonotic transmission of pathogens from NHPs. Identifying such risk groups can contribute to mitigation of not only zoonotic STLV-1 transmission but also transmission of any blood-borne pathogen onto humans in Sub-Saharan Africa.

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“…fected individuals were later reported (28)(29)(30)(31)(32)(33)(34)(35)(36); for a review, see reference 12). While HTLV-1, thanks to its Tax (Tax-1) and HTLV-1 basic leucine zipper (HBZ) proteins, causes leukemia after a long period of clinical latency (37), other HTLVs have not been associated with oncogenic processes.…”

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confidence: 99%

Discovery and Characterization of Auxiliary Proteins Encoded by Type 3 Simian T-Cell Lymphotropic Viruses

Turpin

Journo

et al. 2015

J Virol

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Human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 encode auxiliary proteins that play important roles in viral replication, viral latency, and immune escape. The presence of auxiliary protein-encoding open reading frames (ORFs) in HTLV-3, the latest HTLV to be discovered, is unknown. Simian T-cell lymphotropic virus type 3 (STLV-3) is almost identical to HTLV-3. Given the lack of HTLV-3-infected cell lines, we took advantage of STLV-3-infected cells and of an STLV-3 molecular clone to search for the presence of auxiliary transcripts. Using reverse transcriptase PCR (RT-PCR), we first uncovered the presence of three unknown viral mRNAs encoding putative proteins of 5, 8, and 9 kDa and confirmed the presence of the previously reported RorfII transcript. The existence of these viral mRNAs was confirmed by using splice site-specific RT-PCR with ex vivo samples. We showed that p5 is distributed throughout the cell and does not colocalize with a specific organelle. The p9 localization is similar to that of HTLV-1 p12 and induced a strong decrease in the calreticulin signal, similarly to HTLV-1 p12. Although p8, RorfII, and Rex-3 share an N-terminal sequence that is predicted to contain a nucleolar localization signal (NoLS), only p8 is found in the nucleolus. The p8 location in the nucleolus is linked to a bipartite NoLS. p8 and, to a lesser extent, p9 repressed viral expression but did not alter Rex-3-dependent mRNA export. Using a transformation assay, we finally showed that none of the STLV-3 auxiliary proteins had the ability to induce colony formation, while both Tax-3 and antisense protein of HTLV-3 (APH-3) promoted cellular transformation. Altogether, these results complete the characterization of the newly described primate T-lymphotropic virus type 3 (PTLV-3). IMPORTANCETogether with their simian counterparts, HTLVs form the primate T-lymphotropic viruses. HTLVs arose from interspecies transmission between nonhuman primates and humans. HTLV-1 and HTLV-2 encode auxiliary proteins that play important roles in viral replication, viral latency, and immune escape. The presence of ORFs encoding auxiliary proteins in HTLV-3 or STLV-3 genomes was unknown. Using in silico analyses, ex vivo samples, or in vitro experiments, we have uncovered the presence of 3 previously unknown viral mRNAs encoding putative proteins and confirmed the presence of a previously reported viral transcript. We characterized the intracellular localization of the four proteins. We showed that two of these proteins repress viral expression but that none of them have the ability to induce colony formation. However, both Tax and the antisense protein APH-3 promote cell transformation. Our results allowed us to characterize 4 new retroviral proteins for the first time.

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Identification and Molecular Characterization of New Simian T Cell Lymphotropic Viruses in Nonhuman Primates Bushmeat from the Democratic Republic of Congo

Cited by 22 publications

References 24 publications

High Prevalences and a Wide Genetic Diversity of Simian Retroviruses in Non-human Primate Bushmeat in Rural Areas of the Democratic Republic of Congo

High Prevalences and a Wide Genetic Diversity of Simian Retroviruses in Non-human Primate Bushmeat in Rural Areas of the Democratic Republic of Congo

Bushmeat Hunting and Zoonotic Transmission of Simian T-Lymphotropic Virus 1 in Tropical West and Central Africa

Discovery and Characterization of Auxiliary Proteins Encoded by Type 3 Simian T-Cell Lymphotropic Viruses

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