Differential Outcomes following Optimization of Simian-Human Immunodeficiency Viruses from Clades AE, B, and C.
Animals
Antibodies, Neutralizing
CD4-Positive T-Lymphocytes
Female
Gene Products, env
/ genetics
HIV Infections
/ virology
HIV-1
/ genetics
Humans
Macaca mulatta
Male
Mutation
Sequence Analysis
Simian Acquired Immunodeficiency Syndrome
/ immunology
Simian Immunodeficiency Virus
/ genetics
Viral Load
Virus Replication
Env
HIV-1
SHIV
optimization
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
30
10
2019
accepted:
21
02
2020
pubmed:
7
3
2020
medline:
27
10
2020
entrez:
6
3
2020
Statut:
epublish
Résumé
Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1.
Identifiants
pubmed: 32132241
pii: JVI.01860-19
doi: 10.1128/JVI.01860-19
pmc: PMC7199416
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
Gene Products, env
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI131251
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI131331
Pays : United States
Informations de copyright
Copyright © 2020 Tartaglia et al.
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