Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization

PLoS Pathogens

Carole R. Baskin¹  Bittoo Kanwar¹  David Favre¹  Robert Palermo²  Michael G. Katze²  Sharon Lederer²  Sean Proll²  Kathie-Anne Walters²  Zeljka Kasakow³  Joseph M. McCune⁴ 

[1] Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, California, United States of America;Department of Microbiology, University of Washington, Seattle, Washington, United States of America;Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco, California, United States of America;Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America

关键词: Gene expression;    SIV;    Colon;    Apoptosis;    T cells;    Pathogens;    Blood;    Lymph nodes;   

DOI  :  10.1371/journal.ppat.1000296

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Simian immunodeficiency virus (SIV) infection leads to AIDS in experimentally infected macaques, whereas natural reservoir hosts exhibit limited disease and pathology. It is, however, unclear how natural hosts can sustain high viral loads, comparable to those observed in the pathogenic model, without developing severe disease. We performed transcriptional profiling on lymph node, blood, and colon samples from African green monkeys (natural host model) and Asian pigtailed macaques (pathogenic model) to directly compare gene expression patterns during acute pathogenic versus non-pathogenic SIV infection. The majority of gene expression changes that were unique to either model were detected in the lymph nodes at the time of peak viral load. Results suggest a shift toward cellular stress pathways and Th1 profiles during pathogenic infection, with strong and sustained type I and II interferon responses. In contrast, a strong type I interferon response was initially induced during non-pathogenic infection but resolved after peak viral load. The natural host also exhibited controlled Th1 profiles and better preservation of overall cell homeostasis. This study identified gene expression patterns that are specific to disease susceptibility, tissue compartmentalization, and infection duration. These patterns provide a unique view of how host responses differ depending upon lentiviral infection outcome.

【 授权许可】

CC BY