Novel Transmitted/Founder Simian-Human Immunodeficiency Viruses for Human Immunodeficiency Virus Latency and Cure Research.
Animals
Anti-Retroviral Agents
/ therapeutic use
Disease Models, Animal
HIV Infections
/ complications
HIV-1
/ drug effects
Kinetics
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome
/ complications
Simian Immunodeficiency Virus
/ genetics
Tropism
Viremia
Virus Latency
/ physiology
Virus Replication
/ physiology
env Gene Products, Human Immunodeficiency Virus
HIV
SHIV
animal models
cure
latency
nonhuman primate models
persistence
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
07
10
2019
accepted:
07
01
2020
pubmed:
24
1
2020
medline:
29
9
2020
entrez:
24
1
2020
Statut:
epublish
Résumé
A robust simian-human immunodeficiency virus (SHIV)-macaque model of latency is critical to investigate eradicative and suppressive strategies that target HIV-1 Env. To this end, we previously reported a novel strategy for constructing SHIVs that bear primary or transmitted/founder (TF) Envs with modifications at Env residue 375 that enable efficient replication in Indian rhesus macaques (RM). Such TF SHIVs, however, have not been examined for their suitability for HIV-1 latency and cure research. Here, we evaluate two promising TF SHIVs, SHIV.D.191859 and SHIV.C.CH848, which encode TF subtype D and C HIV-1 Envs, respectively, for their viral kinetics and persistence during suppressive combination antiretroviral therapy (cART) and treatment interruption in RM. Our results suggest that the viral kinetics of these SHIVs in RM during acute, early, and chronic infection, and upon cART initiation, maintenance and discontinuation, mirror those of HIV-1 infection. We demonstrate consistent early peak and set point viremia, rapid declines in viremia to undetectable plasma titers following cART initiation, infection of long-lived cellular subsets and establishment of viral latency, and viral rebound with return to pretreatment set point viremia following treatment interruption. The viral dynamics and reservoir biology of SHIV.D.191859, and to a lesser extent SHIV.C.CH848, during chronic infection, cART administration, and upon treatment interruption suggest that these TF SHIVs are promising reagents for a SHIV model of HIV-1 latency and cure.
Identifiants
pubmed: 31969435
pii: JVI.01659-19
doi: 10.1128/JVI.01659-19
pmc: PMC7108852
pii:
doi:
Substances chimiques
Anti-Retroviral Agents
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI126620
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007632
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI126619
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI045008
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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