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Journal of Virology, July 2005, p. 9217-9227, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9217-9227.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Propagation and Dissemination of Infection after Vaginal Transmission of Simian Immunodeficiency Virus

Christopher J. Miller,1,2,3,4* Qingsheng Li,5 Kristina Abel,1,2 Eun-Young Kim,6 Zhong-Min Ma,1,2 Stephen Wietgrefe,5 Lisa La Franco-Scheuch,1,2 Lara Compton,1,2 Lijie Duan,5 Marta Dykhuizen Shore,5 Mary Zupancic,5 Marc Busch,1,2 John Carlis,5 Steven Wolinksy,6 and Ashley T. Haase5*

Center for Comparative Medicine,1 California National Primate Research Center,2 Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine,3 Department of Infectious Disease, School of Medicine, University of California—Davis, Davis, California 95616,4 Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455,5 Division of Infectious Diseases, The Feinberg School of Medicine at Northwestern University, Chicago, Illinois 606116

Received 5 December 2004/ Accepted 13 April 2005

In the current global AIDS pandemic, more than half of new human immunodeficiency virus type 1 (HIV-1) infections are acquired by women through intravaginal HIV exposure. For this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using an animal model in which female rhesus macaques were exposed intravaginally to a high dose of simian immunodeficiency virus (SIV). We examined in detail the events that transpire from hours to a few days after intravaginal SIV exposure through week 4 to provide a framework for understanding the propagation, dissemination, and establishment of infection in lymphatic tissues (LTs) during the acute stage of infection. We show that the mucosal barrier greatly limits the infection of cervicovaginal tissues, and thus the initial founder populations of infected cells are small. While there was evidence of rapid dissemination to distal sites, we also show that continuous seeding from an expanding source of production at the portal of entry is likely critical for the later establishment of a productive infection throughout the systemic LTs. The initially small founder populations and dependence on continuous seeding to establish a productive infection in systemic LTs define a small window of maximum vulnerability for the virus in which there is an opportunity for the host, vaccines, or other interventions to prevent or control infection.


* Corresponding author. Mailing address for Christopher J. Miller: California National Primate Research Center, One Shields Ave., Davis, CA 95616. Phone: (530) 752-8584. Fax: (530) 752-2880. E-mail: cjmiller{at}ucdavis.edu. Mailing address for Ashley T. Haase: Department of Microbiology, University of Minnesota, MMC 196, 420 Delaware Street S.E., Minneapolis, MN 55455. Phone: (612) 624-4442. Fax: (612) 626-0623. E-mail: haase001{at}umn.edu.


Journal of Virology, July 2005, p. 9217-9227, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.9217-9227.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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