Immune Responses and Viral Persistence in Simian/Human Immunodeficiency Virus SHIV.C.CH848-Infected Rhesus Macaques

Autor: Katharine J. Bar, Xiaolei Wang, Ronald S. Veazey, Huanbin Xu, Widade Ziani, Hong Lu, Hui Li, Dongfang Liu, Anya M. Bauer, George M. Shaw, Xueling Wu
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
animal diseases
viruses
Immunology
Simian Acquired Immunodeficiency Syndrome
HIV Infections
Viremia
Biology
Simian
medicine.disease_cause
Microbiology
03 medical and health sciences
Immune system
Virology
evolution
medicine
Animals
Humans
Immunodeficiency
030304 developmental biology
persistent infection
0303 health sciences
030306 microbiology
autologous neutralizing Abs and evolution
virus diseases
Viral Load
Simian immunodeficiency virus
medicine.disease
biology.organism_classification
Antibodies
Neutralizing
Macaca mulatta
viral reservoirs
humanities
autologous neutralizing Abs
Disease Models
Animal
Anti-Retroviral Agents
SHIV
Viral replication
Insect Science
Viral evolution
HIV-1
biology.protein
Pathogenesis and Immunity
Simian Immunodeficiency Virus
Antibody
Zdroj: Journal of Virology
ISSN: 1098-5514
0022-538X
Popis: SHIVs have been extensively used in a nonhuman primate (NHP) model for HIV research. In this study, we investigated viral reservoirs in tissues and immune responses in an NHP model inoculated with newly generated transmitted/founder HIV-1 clade C-based SHIV.C.CH848.
Chimeric simian/human immunodeficiency viruses (SHIVs) are widely used in nonhuman primate models to recapitulate human immunodeficiency virus (HIV) infection in humans, yet most SHIVs fail to establish persistent viral infection. We investigated immunological and virological events in rhesus macaques infected with the newly developed SHIV.C.CH848 (SHIVC) and treated with combined antiretroviral therapy (cART). Similar to HIV/simian immunodeficiency virus (SIV) infection, SHIV.C.CH848 infection established viral reservoirs in CD4+ T cells and myeloid cells, accompanied by productive infection and depletion of CD4+ T cells in systemic and lymphoid tissues throughout SHIV infection. Despite 6 months of cART-suppressed viral replication, integrated proviral DNA levels remained stable, especially in CD4+ T cells, and the viral rebound was also observed after ART interruption. Autologous neutralizing antibodies to the parental HIV-1 strain CH848 were detected, with limited viral evolution at 5 months postinfection. In comparison, heterogenous neutralizing antibodies in SHIV.C.CH848-infected macaques were not detected except for 1 (1 of 10) animal at 2 years postinfection. These findings suggest that SHIV.C.CH848, a novel class of transmitted/founder SHIVs, can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research. IMPORTANCE SHIVs have been extensively used in a nonhuman primate (NHP) model for HIV research. In this study, we investigated viral reservoirs in tissues and immune responses in an NHP model inoculated with newly generated transmitted/founder HIV-1 clade C-based SHIV.C.CH848. The data show that transmitted founder (T/F) SHIVC infection of macaques more closely recapitulates the virological and clinical features of HIV infection, including persistent viremia and viral rebound once antiretroviral therapy is discontinued. These results suggest this CCR5-tropic, SHIVC strain is valuable for testing responses to HIV vaccines and therapeutics.
Databáze: OpenAIRE
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