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Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

ABSTRACT: One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8- and anti-CD20 lymphocyte-depleting antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before challenge with SIV(sab9315BR). In vivo lymphocyte depletion during primary infection resulted in a brief elevation of viremia but not in disease. Based on the magnitude and timing of SIV-specific CD8(+) T-cell responses in the lymphocyte-depleted animals, CD8(+) T-cell responses appear to contribute to viral containment in natural hosts. We found no evidence for a contribution of humoral immune responses in viral containment. These studies indicate that natural hosts have developed mechanisms in addition to classic adaptive immune responses to cope with this lentiviral infection. Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection.

SUBMITTER: Zahn RC

PROVIDER: S-EPMC2858477 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

Zahn Roland C RC Rett Melisa D MD Li Ming M Tang Haili H Korioth-Schmitz Birgit B Balachandran Harikrishnan H White Robert R Pryputniewicz Sarah S Letvin Norman L NL Kaur Amitinder A Montefiori David C DC Carville Angela A Hirsch Vanessa M VM Allan Jonathan S JS Schmitz Jörn E JE

Blood 20100210 15

One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8- ...[more]

PMID: 20147699

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Project description:Unlike HIV infection, SIV infection is generally nonpathogenic in natural hosts, such as African green monkeys (AGMs), despite life-long high viral replication. Lack of disease progression was reportedly based on the ability of SIV-infected AGMs to prevent gut dysfunction, avoiding microbial translocation and the associated systemic immune activation and chronic inflammation. Yet, the maintenance of gut integrity has never been documented, and the mechanism(s) by which gut integrity is preserved are unknown. We sought to investigate the early events of SIV infection in AGMs, specifically examining the impact of SIVsab infection on the gut mucosa. Twenty-nine adult male AGMs were intrarectally infected with SIVsab92018 and serially sacrificed at well-defined stages of SIV infection, preramp-up (1-3 days post-infection (dpi)), ramp-up (4-6 dpi), peak viremia (9-12 dpi), and early chronic SIV infection (46-55 dpi), to assess the levels of immune activation, apoptosis, epithelial damage and microbial translocation in the GI tract and peripheral lymph nodes. Tissue viral loads, plasma cytokines and plasma markers of gut dysfunction were also measured throughout the course of early infection. While a strong, but transient, interferon-based inflammatory response was observed, the levels of plasma markers linked to enteropathy did not increase. Accordingly, no significant increases in apoptosis of either mucosal enterocytes or lymphocytes, and no damage to the mucosal epithelium were documented during early SIVsab infection of AGMs. These findings were supported by RNAseq of the gut tissue, which found no significant alterations in gene expression that would indicate microbial translocation. Thus, for the first time, we confirmed that gut epithelial integrity is preserved, with no evidence of microbial translocation, in AGMs throughout early SIVsab infection. This might protect AGMs from developing intestinal dysfunction and the subsequent chronic inflammation that drives both HIV disease progression and HIV-associated comorbidities.

Dataset Information

Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

Publications

Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

Similar Datasets

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