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

Author:

Bar Katharine J.1,Coronado Ernesto23,Hensley-McBain Tiffany23,O’Connor Megan A.34,Osborn Jessica M.34,Miller Charlene235,Gott Toni M.23,Wangari Solomon3,Iwayama Naoto3,Ahrens Chul Y.3,Smedley Jeremy36,Moats Cassie36,Lynch Rebecca M.7,Haddad Elias K.8,Haigwood Nancy L.6,Fuller Deborah H.34,Shaw George M.1,Klatt Nichole R.235,Manuzak Jennifer A.235ORCID

Affiliation:

1. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

2. Department of Pharmaceutics, University of Washington, Seattle, Washington, USA

3. Washington National Primate Research Center, University of Washington, Seattle, Washington, USA

4. Department of Microbiology, University of Washington, Seattle, Washington, USA

5. Department of Pediatrics, Miller School of Medicine, University of Miami, Miami, Florida, USA

6. Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, USA

7. Department of Microbiology, Immunology and Tropical Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA

8. Division of Infectious Diseases & HIV Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

Abstract

The development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing for in vivo 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.

Funder

Penn Center for AIDS Research Viral and Molecular Core

BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy

CARE: Delaney Collaboratory for AIDS Eradication

National Institutes of Health Office of the Director

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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