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Sui Yongjun; Dzutsev, Amiran; Venzon, David; Frey, Blake; Trinchieri, Giorgio; Berzofsky, Jay
JAIDS Journal of Acquired Immune Deficiency Syndromes: January 2016
doi: 10.1097/01.qai.0000479706.78821.e3
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The role of commensal bacteria in modulating immune activation in the gastrointestinal (GI) tract is largely unknown. As the risk of HIV-acquisition is increased by gut immune activation, we indeed observed that 2 cohorts of naïve Indian rhesus macaques from 2 separate sources, which had different rectal immune activation, demonstrated significantly different challenge outcomes in our recent repeated low-dose intrarectal simian-human immunodeficiency virus (SHIV) challenge study. The[LINE SEPARATOR]rectal mucosal immune activation correlated inversely with the number[LINE SEPARATOR]of intrarectal exposures needed for viral infection. To assess whether microbial communities account for this non-pathogen-associated GI immune activation and the susceptibility to SHIV exposure, we examined the gut microbiome by 16S rRNA MiSeq using the fecal samples[LINE SEPARATOR]collected 1 week before the serial challenges. The preliminary principal component analysis of the gut taxa showed that these two cohorts had different microbial compositions even after more than 5 months of co- housing. A compositional look at gut taxa revealed down-regulation of the ratio of bacteroides to prevotella in the more susceptible cohort, similar[LINE SEPARATOR]to that previously observed in HIV-infected patients. Furthermore, local immune activation might be influenced by specific gut bacteria, such as firmicutes, which were found more abundantly in the resistant cohort,[LINE SEPARATOR]and inversely correlated with the frequency of Ki67+CCR5+CD4+T cells (SHIV target cells) in the rectal mucosa. Detailed analysis and potential confirmatory studies are underway. This study can provide novel insights into the microbiome-host interactions, and thus pave the way for potential strategies to reduce susceptibility to HIV-1 transmission.

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