Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection

Xing Pei Hao, Carissa M. Lucero, Baris Turkbey, Marcelino L. Bernardo, David R. Morcock, Claire Deleage, Charles M. Trubey, Jeremy Smedley, Nichole R. Klatt, Luis D. Giavedoni, Jan Kristoff, Amy Xu, Gregory Q. Del Prete, Brandon F. Keele, Srinivas S. Rao, W. Gregory Alvord, Peter L. Choyke, Jeffrey D. Lifson, Jason M. Brenchley, Cristian Apetrei, Ivona Pandrea and Jacob D. Estes ()
Additional contact information
Xing Pei Hao: Pathology and Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Carissa M. Lucero: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Baris Turkbey: Molecular Imaging Program, National Cancer Institute
Marcelino L. Bernardo: Molecular Imaging Program, National Cancer Institute
David R. Morcock: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Claire Deleage: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Charles M. Trubey: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Jeremy Smedley: Laboratory Animal Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Nichole R. Klatt: WaNPRC, University of Washington
Luis D. Giavedoni: Southwest National Primate Research Center, Texas Biomedical Research Institute
Jan Kristoff: Center for Vaccine Research, University of Pittsburgh
Amy Xu: Center for Vaccine Research, University of Pittsburgh
Gregory Q. Del Prete: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Brandon F. Keele: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Srinivas S. Rao: Laboratory Animal Medicine, Vaccine Research Center, NIAID, NIH
W. Gregory Alvord: Statistical Consulting, Data Management Services, Inc., National Cancer Institute at Frederick
Peter L. Choyke: Molecular Imaging Program, National Cancer Institute
Jeffrey D. Lifson: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research
Jason M. Brenchley: Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH
Cristian Apetrei: Center for Vaccine Research, University of Pittsburgh
Ivona Pandrea: Center for Vaccine Research, University of Pittsburgh
Jacob D. Estes: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: Abstract Mucosal damage to the gastrointestinal (GI) tract with resulting microbial translocation is hypothesized to significantly contribute to the heightened and persistent chronic inflammation and immune activation characteristic to HIV infection. Here we employ a non-human primate model of chemically induced colitis in SIV-uninfected rhesus macaques that we developed using dextran sulfate sodium (DSS), to directly test this hypothesis. DSS treatment results in GI barrier damage with associated microbial translocation, inflammation and immune activation. The progression and severity of colitis are longitudinally monitored by a magnetic resonance imaging approach. DSS treatment of SIV-infected African green monkeys, a natural host species for SIV that does not manifest GI tract damage or chronic immune activation during infection, results in colitis with elevated levels of plasma SIV RNA, sCD14, LPS, CRP and mucosal CD4+ T-cell loss. Together these results support the hypothesis that GI tract damage leading to local and systemic microbial translocation, and associated immune activation, are important determinants of AIDS pathogenesis.

Date: 2015
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DOI: 10.1038/ncomms9020

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