Simian Immunodeficiency Virus–Induced Intestinal Cell Apoptosis Is the Underlying Mechanism of the Regenerative Enteropathy of Early Infection

Authors

Qingsheng Li, University of Minnesota, MinneapolisFollow
Jacob D. Estes, University of Minnesota, MinneapolisFollow
Lijie Duan, University of Minnesota, MinneapolisFollow
Jose Jessurun, University of Minnesota, Minneapolis
Stefan Pambuccian, University of Minnesota, Minneapolis
Colleen Forster, University of Minnesota, Minneapolis
Stephen Wietgrefe, University of Minnesota, MinneapolisFollow
Mary Zupancic, University of Minnesota, Minneapolis
Timothy Schacker, University of Minnesota, Minneapolis
Cavan Reilly, University of Minnesota, MinneapolisFollow
John V. Carlis, University of Minnesota, Minneapolis
Ashley T. Haase, University of Minnesota, MinneapolisFollow

Date of this Version

2008

Document Type

Article

Citation

The Journal of Infectious Diseases 197 (2008), pp. 420–429. doi: 10.1086/525046

Comments

Copyright © 2008 Infectious Diseases Society of America. Used by permission.

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.