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Genetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity

dc.rights.licenseopenen_US
dc.contributor.authorLE HINGRAT, Q.
dc.contributor.authorVISSEAUX, B.
dc.contributor.authorBERTINE, M.
dc.contributor.authorCHAUVEAU, L.
dc.contributor.authorSCHWARTZ, O.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCOLLIN, Fideline
dc.contributor.authorDAMOND, F.
dc.contributor.authorMATHERON, S.
dc.contributor.authorDESCAMPS, D.
dc.contributor.authorCHARPENTIER, C.
dc.date.accessioned2021-02-02T15:35:23Z
dc.date.available2021-02-02T15:35:23Z
dc.date.issued2020
dc.identifier.issn0022-538X (Print) 0022-538xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26096
dc.description.abstractEnThe HIV-2 long terminal repeat (LTR) region contains several transcription factor (TF) binding sites. Efficient LTR transactivation by cellular TF and viral proteins is crucial for HIV-2 reactivation and viral production. Proviral LTRs from 66 antiretroviral-naive HIV-2-infected patients included in the French ANRS HIV-2 CO5 Cohort were sequenced. High genetic variability within the HIV-2 LTR was observed, notably in the U3 subregion, the subregion encompassing most known TF binding sites. Genetic variability was significantly higher in HIV-2 group B than in group A viruses. Notably, all group B viruses lacked the peri-ETS binding site, and 4 group B sequences (11%) also presented a complete deletion of the first Sp1 binding site. The lack of a peri-ETS binding site was responsible for lower transcriptional activity in activated T lymphocytes, while deletion of the first Sp1 binding site lowered basal or Tat-mediated transcriptional activities, depending on the cell line. Interestingly, the HIV-2 cellular reservoir was less frequently quantifiable in patients infected by group B viruses and, when quantifiable, the reservoirs were significantly smaller than in patients infected by group A viruses. Our findings suggest that mutations observed in vivo in HIV-2 LTR sequences are associated with differences in transcriptional activity and may explain the small cellular reservoirs in patients infected by HIV-2 group B, providing new insight into the reduced pathogenicity of HIV-2 infection. IMPORTANCE Over 1 million patients are infected with HIV-2, which is often described as an attenuated retroviral infection. Patients frequently have undetectable viremia and evolve at more slowly toward AIDS than HIV-1-infected patients. Several studies have reported a smaller viral reservoir in peripheral blood mononuclear cells in HIV-2-infected patients than in HIV-1-infected patients, while others have found similar sizes of reservoirs but a reduced amount of cell-associated RNA, suggesting a block in HIV-2 transcription. Recent studies have found associations between mutations within the HIV-1 LTR and reduced transcriptional activities. Until now, mutations within the HIV-2 LTR region have scarcely been studied. We conducted this research to discover if such mutations exist in the HIV-2 LTR and their potential association with the viral reservoir and transcriptional activity. Our study indicates that transcription of HIV-2 group B proviruses may be impaired, which might explain the small viral reservoir observed in patients.
dc.language.isoENen_US
dc.subjectSISTM
dc.title.enGenetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity
dc.title.alternativeJ Virolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1128/jvi.01504-19en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31915276en_US
bordeaux.journalJournal of Virologyen_US
bordeaux.volume94en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamSISTM_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03129135
hal.version1
hal.date.transferred2021-02-02T15:35:27Z
hal.exporttrue
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