Open AccessGenetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity
Author(s) -
Quentin Le Hingrat,
Benoît Visseaux,
Mélanie Bertine,
Lise Chauveau,
Olivier Schwartz,
Fidéline Collin,
Florence Damond,
Sophie Matheron,
Diane Descamps,
Charlotte Charpentier
Publication year - 2020
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01504-19
Subject(s) - long terminal repeat , viremia , biology , peripheral blood mononuclear cell , virology , transcription (linguistics) , human immunodeficiency virus (hiv) , lentivirus , viral replication , genetics , immunology , viral disease , gene , virus , gene expression , in vitro , linguistics , philosophy
The 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.