Experimental colitis in SIV-uninfected rhesus macaques recapitulates important features of pathogenic SIV infection.
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.
Pathology and Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 539, Post Office Box B, Frederick, Maryland 21702, USA.
Xing Pei
XP
Hao
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Carissa M
CM
Lucero
Molecular Imaging Program, National Cancer Institute, Building 10, Room B3B69F, Bethesda, Maryland 20814, USA.
Baris
B
Turkbey
Molecular Imaging Program, National Cancer Institute, Building 10, Room B3B69F, Bethesda, Maryland 20814, USA.
Marcelino L
ML
Bernardo
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
David R
DR
Morcock
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Claire
C
Deleage
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Charles M
CM
Trubey
1] Laboratory Animal Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 14D RM 233, 14 Service RD West, Bethesda, Maryland 20814, USA [2] Washington National Primate Research Center, University of Washington, 1705 NE Pacific Street, Box 357330, Seattle, Washington 98195, USA.
Jeremy
J
Smedley
Department of Pharmaceutics, WaNPRC, University of Washington, 3018 Western Avenue, Box 357331, Seattle, Washington 98121, USA.
Nichole R
NR
Klatt
Department of Virology and Immunology, Southwest National Primate Research Center, Texas Biomedical Research Institute, 7620 NW Loop 410, San Antonio, Texas 78227, USA.
Luis D
LD
Giavedoni
1] Center for Vaccine Research, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA [2] School of Public Health, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA.
Jan
J
Kristoff
1] Center for Vaccine Research, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA [2] Department of Microbiology and Molecular Genetics, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA.
Amy
A
Xu
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Gregory Q
GQ
Del Prete
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Brandon F
BF
Keele
Laboratory Animal Medicine, Vaccine Research Center, NIAID, NIH, BG 40, 40 Convent Drive, Bethesda, Maryland 20814, USA.
Srinivas S
SS
Rao
Statistical Consulting, Data Management Services, Inc., National Cancer Institute at Frederick, Post Office Box B, Frederick, Maryland 21702, USA.
W Gregory
WG
Alvord
Molecular Imaging Program, National Cancer Institute, Building 10, Room B3B69F, Bethesda, Maryland 20814, USA.
Peter L
PL
Choyke
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Jeffrey D
JD
Lifson
Immunopathogenesis Section, Lab of Molecular Microbiology, NIAID, NIH, BG 4 RM 201, 4 Memorial Drive, Bethesda, Maryland 20814, USA.
Jason M
JM
Brenchley
1] Center for Vaccine Research, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA [2] Department of Microbiology and Molecular Genetics, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA.
Cristian
C
Apetrei
1] Center for Vaccine Research, University of Pittsburgh, 9044 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA [2] Department of Pathology and School of Medicine, University of Pittsburgh, 9017 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, USA.
Ivona
I
Pandrea
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, BG 535, Post Office Box B, Frederick, Maryland 21702, USA.
Jacob D
JD
Estes
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D041981:Gastrointestinal Tract / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology*; D015302:Simian Immunodeficiency Virus
D016264:Dextran Sulfate