Logo image
Back
Simian-Human Immunodeficiency Virus SHIV.CH505 Infection of Rhesus Macaques Results in Persistent Viral Replication and Induces Intestinal Immunopathology
Journal article   Open access   Peer reviewed

Simian-Human Immunodeficiency Virus SHIV.CH505 Infection of Rhesus Macaques Results in Persistent Viral Replication and Induces Intestinal Immunopathology

Katharine J Bar, Ernesto Coronado, Tiffany Hensley-McBain, Megan A O'Connor, Jessica M Osborn, Charlene Miller, Toni M Gott, Solomon Wangari, Naoto Iwayama, Chul Y Ahrens, …
Journal of virology, v 93(18)
15 Sep 2019
DOI: https://doi.org/10.1128/JVI.00372-19
PMID: 31217249
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.00372-19View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1128/JVI.00372-19View
Published, Version of Record (VoR) Open

Abstract

Animals Disease Models, Animal env Gene Products, Human Immunodeficiency Virus - genetics env Gene Products, Human Immunodeficiency Virus - immunology Genetic Engineering - methods HIV - immunology HIV Infections - virology HIV-1 - immunology Humans Intestinal Mucosa - metabolism Intestinal Mucosa - virology Macaca mulatta - virology Models, Biological Simian Acquired Immunodeficiency Syndrome - virology Simian Immunodeficiency Virus - immunology Viral Load - immunology Virus Replication - physiology
Simian-human immunodeficiency viruses (SHIVs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. However, the majority of SHIVs currently available have significant limitations in that they were developed using sequences from chronically HIV-infected individuals or uncommon HIV subtypes or were optimized for the macaque model by serially passaging the engineered virus or Recently, a newly developed SHIV, SHIV.C.CH505.375H.dCT (SHIV.CH505), which incorporates vpu-env (gp140) sequences from a transmitted/founder HIV-1 subtype C strain, was shown to retain attributes of primary HIV-1 strains. However, a comprehensive analysis of the immunopathology that results from infection with this virus, especially in critical tissue compartments like the intestinal mucosa, has not been completed. In this study, we evaluated the viral dynamics and immunopathology of SHIV.CH505 in rhesus macaques. In line with previous findings, we found that SHIV.CH505 is capable of infecting and replicating efficiently in rhesus macaques, resulting in peripheral viral kinetics similar to that seen in pathogenic SIV and HIV infection. Furthermore, we observed significant and persistent depletions of CCR5 and CCR6 CD4 T cells in mucosal tissues, decreases in CD4 T cells producing Th17 cell-associated cytokines, CD8 T cell dysfunction, and alterations of B cell and innate immune cell function, indicating that SHIV.CH505 elicits intestinal immunopathology typical of SIV/HIV infection. These findings suggest that SHIV.CH505 recapitulates the early viral replication dynamics and immunopathogenesis of HIV-1 infection of humans and thus can serve as a new model for HIV-1 pathogenesis, treatment, and prevention research. The development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing for testing of novel treatments. However, many of the currently available SHIVs have distinct drawbacks and are unable to fully reflect the features characteristic of primary SIV and HIV strains. Here, we utilize rhesus macaques to define the immunopathogenesis of the recently developed SHIV.CH505, which was designed without many of the limitations of previous SHIVs. We observed that infection with SHIV.CH505 leads to peripheral viral kinetics and mucosal immunopathogenesis comparable with those caused by pathogenic SIV and HIV. Overall, these data provide evidence of the value of SHIV.CH505 as an effective model of SIV/HIV infection and an important tool that can be used in future studies, including preclinical testing of new therapies or prevention strategies.

Metrics

8 Record Views
29 citations in Web of Science
28 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
Web of Science research areas
Virology
Logo image