Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus.
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.
Miller
Christopher J
CJ
Center for Comparative Medicine, University of California-Davis, Davis, CA 95616, USA. cjmiller@ucdavis.edu
Li
Qingsheng
Q
Abel
Kristina
K
Kim
Eun-Young
EY
Ma
Zhong-Min
ZM
Wietgrefe
Stephen
S
La Franco-Scheuch
Lisa
L
Compton
Lara
L
Duan
Lijie
L
Shore
Marta Dykhuizen
MD
Zupancic
Mary
M
Busch
Marc
M
Carlis
John
J
Wolinsky
Steven
S
Wolinksy
Steven
S
Haase
Ashley T
AT
D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D008221:Lymphoid Tissue / Q000821:virology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis; D018449:SAIDS Vaccines / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification*; D014621:Vagina / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication
D004279:DNA, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines