A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption.
Anti-Retroviral Agents
/ pharmacology
Antiretroviral Therapy, Highly Active
Biological Clocks
/ genetics
CD4-Positive T-Lymphocytes
/ pathology
HIV Infections
/ genetics
HIV Seropositivity
HIV-1
/ genetics
Humans
Macrophages
/ immunology
Proviruses
/ genetics
Viral Load
/ genetics
Viremia
/ genetics
HIV-1 reservoirs
analytical treatment interruption
macrophages
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
pubmed:
18
4
2020
medline:
29
7
2020
entrez:
18
4
2020
Statut:
ppublish
Résumé
HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses constructed with individual envelope genes that were obtained from plasma of six individuals undergoing analytic treatment interruption (ATI). M-tropic viruses could also be enriched from post-ATI plasma using macrophage-specific (CD14) but not CD4+ T cell-specific (CD3) antibodies, suggesting that M-tropic viruses had a macrophage origin. Molecular clock analysis indicated that the establishment of M-tropic HIV-1 variants predated ATI. Collectively, these data suggest that macrophages are a viral reservoir in HIV-1-infected individuals on effective ART and that M-tropic variants can appear in rebounding viremia when treatment is interrupted. These findings have implications for the design of curative strategies for HIV-1.
Identifiants
pubmed: 32300019
pii: 1917034117
doi: 10.1073/pnas.1917034117
pmc: PMC7211992
doi:
Substances chimiques
Anti-Retroviral Agents
0
Banques de données
GENBANK
['MK250122', 'MK250216', 'MK250217', '250273', 'MK250274', 'MK250362', 'MK254784', 'MK254839', 'MN395385', 'MK250100', 'MK250121', 'MK254843', 'MK254890', 'MK254895', 'MK254897', 'MK254911', 'MK254912', 'MK254914', 'MK254952', 'MK254959', 'MK254964', 'MK254967']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
9981-9990Subventions
Organisme : NIMH NIH HHS
ID : R01 MH116701
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI073961
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS063897
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI131568
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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