title: Marked Enteropathy in an Accelerated Macaque Model of AIDS.
abstract: Enteropathy in HIV infection is not eliminated with combination antiretroviral therapy and is possibly linked to microbial translocation. We used a rapidly progressing SIV/pigtailed macaque model of HIV to examine enteropathy and microbial translocation. Histologic evidence of intestinal disease was observed in only half of infected macaques during late-stage infection (LSI). Combination antiretroviral therapy initiated during acute infection prevented intestinal disease. In the ileum and colon, enteropathy was associated with increased caspase-3 staining, decreased CD3+T cells, and increased SIV-infected cells. CD3+T cells were preserved in LSI animals without intestinal disease, and levels of CD3 staining in all LSI animals strongly correlated with the number of infected cells in the intestine and plasma viral load. Unexpectedly, there was little evidence of microbial translocation as measured by soluble CD14, soluble CD163, lipopolysaccharide binding protein, and microbial 16s ribosomal DNA. Loss of epithelial integrity indicated by loss of the tight junction protein claudin-3 was not observed during acute infection despite significantly fewer T cells. Claudin-3 was reduced in LSI animals with severe intestinal disease but did not correlate with increased microbial translocation. LSI animals that did not develop intestinal disease had increased T-cell intracytoplasmic antigen 1-positive cytotoxic T lymphocytes, suggesting a robust adaptive cytotoxic T-lymphocyte response may, in part, confer resilience to SIV-induced intestinal damage.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: jcrotea1@jhmi.edu.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Croteau
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Engle
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Queen
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Erin N
authors.initials: EN
authors.lastname: Shirk
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: M Christine
authors.initials: MC
authors.lastname: Zink
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology*; D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D053148:Caspase 3 / Q000378:metabolism; D062465:Claudin-3 / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000378:metabolism; D019053:HIV Enteropathy / Q000097:blood / Q000473:pathology* / Q000821:virology; D007082:Ileum / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D007422:Intestines / Q000473:pathology; D008253:Macaca mulatta; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D062465:Claudin-3; D039102:Poly(A)-Binding Proteins; D053148:Caspase 3