title: Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection.
abstract: The enteropathic manifestations of the human immunodeficiency virus (HIV) and the simian immunodeficiency virus (SIV) in late infection are usually due to infection by other microbes, but in early infection the viruses themselves cause an enteropathy by heretofore undetermined mechanisms. Here we report that SIV induces massive apoptosis of intestinal epithelial cells lining the small and large bowel, thus identifying apoptosis as the driving force behind the regenerative pathology of early infection. We found that apoptosis of gut epithelium paralleled the previously documented apoptosis and massive depletion of CD4 T cells in gut lamina propria, triggered by established mechanisms of gut epithelial cell apoptosis and, at peak, possibly by virus interactions with GPR15/Bob, an intestinal epithelial cell-associated alternative coreceptor for SIV and HIV-1. Apoptosis in early SIV infection is thus the common theme of the pathological processes that quickly afflict the innate as well as adaptive arms of the gut immune system.
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.forename: Jose
authors.initials: J
authors.lastname: Jessurun
authors.forename: Stefan
authors.initials: S
authors.lastname: Pambuccian
authors.forename: Colleen
authors.initials: C
authors.lastname: Forster
authors.forename: Stephen
authors.initials: S
authors.lastname: Wietgrefe
authors.forename: Mary
authors.initials: M
authors.lastname: Zupancic
authors.forename: Timothy
authors.initials: T
authors.lastname: Schacker
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.forename: John V
authors.initials: JV
authors.lastname: Carlis
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000473:pathology / Q000821:virology*; D007420:Intestine, Large / Q000473:pathology / Q000821:virology*; D007421:Intestine, Small / Q000473:pathology / Q000821:virology*; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D012038:Regeneration; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity