PMID- 38464135
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240320
DP  - 2024 Feb 19
TI  - Metformin Enhances Antibody-Mediated Recognition of HIV-Infected CD4(+) T-Cells 
      by Decreasing Viral Release.
LID - 2024.02.15.580166 [pii]
LID - 10.1101/2024.02.15.580166 [doi]
AB  - The mechanistic target of rapamycin (mTOR) positively regulates multiple steps of 
      the HIV-1 replication cycle. We previously reported that a 12-weeks 
      supplementation of antiretroviral therapy (ART) with metformin, an indirect mTOR 
      inhibitor used in type-2 diabetes treatment, reduced mTOR activation and HIV 
      transcription in colon-infiltrating CD4(+) T-cells, together with systemic 
      inflammation in nondiabetic people with HIV-1 (PWH). Herein, we investigated the 
      antiviral mechanisms of metformin. In a viral outgrowth assay performed with 
      CD4(+) T-cells from ART-treated PWH, and upon infection in vitro with 
      replication-competent and VSV-G-pseudotyped HIV-1, metformin decreased virion 
      release, but increased the frequency of productively infected CD4(low)HIV-p24(+) 
      T-cells. These observations coincided with increased BST2/Tetherin (HIV release 
      inhibitor) and Bcl-2 (pro-survival factor) expression, and improved recognition 
      of productively infected T-cells by HIV-1 Envelope antibodies. Thus, metformin 
      exerts pleiotropic effects on post-transcription/translation steps of the HIV-1 
      replication cycle and may be used to accelerate viral reservoir decay in 
      ART-treated PWH.
FAU - Fert, Augustine
AU  - Fert A
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
FAU - Richard, Jonathan
AU  - Richard J
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
FAU - Marchand, Laurence Raymond
AU  - Marchand LR
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
FAU - Planas, Delphine
AU  - Planas D
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
FAU - Routy, Jean-Pierre
AU  - Routy JP
AD  - Infectious Diseases and Immunity in Global Health Program, Research Institute, 
      McGill University Health Centre, Montreal, QC, Canada.
AD  - Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, 
      Canada.
AD  - Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.
FAU - Chomont, Nicolas
AU  - Chomont N
AUID- ORCID: 0000-0001-9747-5018
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
FAU - Finzi, Andres
AU  - Finzi A
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
FAU - Ancuta, Petronela
AU  - Ancuta P
AUID- ORCID: 0000-0003-1922-5640
AD  - Centre de recherche du Centre hospitalier de l'Universite de Montreal, Montreal, 
      QC, H2X 0A9, Canada.
AD  - Departement de microbiologie, infectiologie et immunologie, Faculte de medecine, 
      Universite de Montreal, Montreal, QC, H3C 3J7, Canada.
AD  - Lead Contact.
LA  - eng
GR  - R01 AI148379/AI/NIAID NIH HHS/United States
GR  - R01 AI150322/AI/NIAID NIH HHS/United States
GR  - UM1 AI164560/AI/NIAID NIH HHS/United States
GR  - UM1 AI164562/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20240219
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10925111
COIS- CONFLICT OF INTEREST The authors declare no competing interests.
EDAT- 2024/03/11 06:43
MHDA- 2024/03/11 06:44
PMCR- 2024/03/10
CRDT- 2024/03/11 04:31
PHST- 2024/03/11 06:43 [pubmed]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/03/11 04:31 [entrez]
PHST- 2024/03/10 00:00 [pmc-release]
AID - 2024.02.15.580166 [pii]
AID - 10.1101/2024.02.15.580166 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Feb 19:2024.02.15.580166. doi: 
      10.1101/2024.02.15.580166.