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Tytuł pozycji:

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

Tytuł:
Genetic Variability of Long Terminal Repeat Region between HIV-2 Groups Impacts Transcriptional Activity.
Autorzy:
Le Hingrat Q; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France .; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Visseaux B; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Bertine M; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Chauveau L; Institut Pasteur, Unité Virus et Immunité, Paris, France.
Schwartz O; Institut Pasteur, Unité Virus et Immunité, Paris, France.
Collin F; ISPED, UMR 897, INSERM, Université Bordeaux, Epidémiologie-Biostatistique, Bordeaux, France.
Damond F; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Matheron S; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Service de Maladies Infectieuses et Tropicales, AP-HP, Hôpital Bichat, Paris, France.
Descamps D; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Charpentier C; Université de Paris, IAME, UMR 1137, IINSERM, Paris, France.; Laboratoire de Virologie, AP-HP, Hôpital Bichat, Paris, France.
Źródło:
Journal of virology [J Virol] 2020 Mar 17; Vol. 94 (7). Date of Electronic Publication: 2020 Mar 17 (Print Publication: 2020).
Typ publikacji:
Comparative Study; Journal Article
Język:
English
Imprint Name(s):
Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.
MeSH Terms:
Gene Expression Regulation, Viral*
Genetic Variation*
HIV Infections/*virology
HIV Long Terminal Repeat/*genetics
HIV-2/*genetics
Binding Sites ; Female ; France/epidemiology ; Gene Deletion ; HEK293 Cells ; Humans ; Leukocytes, Mononuclear/virology ; Male ; Middle Aged ; Mutation ; Phylogeny ; Proviruses/genetics ; Transcription, Genetic ; tat Gene Products, Human Immunodeficiency Virus/genetics
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Contributed Indexing:
Keywords: ETS transcription factors; human immunodeficiency virus; long terminal repeat; transcription factors
Substance Nomenclature:
0 (tat Gene Products, Human Immunodeficiency Virus)
Entry Date(s):
Date Created: 20200110 Date Completed: 20200914 Latest Revision: 20200917
Update Code:
20240105
PubMed Central ID:
PMC7081896
DOI:
10.1128/JVI.01504-19
PMID:
31915276
Czasopismo naukowe
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.
(Copyright © 2020 American Society for Microbiology.)

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