title: Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract.
abstract: The majority of new HIV infections occur in women as a result of heterosexual intercourse, overcoming multiple innate barriers to infection within the mucosa. However, the avenues through which infection is established, and the nature of bottlenecks to transmission, have been the source of considerable investigation and contention. Using a high dose of a single round non-replicating SIV-based vector containing a novel dual reporter system, we determined the sites of infection by the inoculum using the rhesus macaque vaginal transmission model. Here we show that the entire female reproductive tract (FRT), including the vagina, ecto- and endocervix, along with ovaries and local draining lymph nodes can contain transduced cells only 48 hours after inoculation. The distribution of infection shows that virions quickly disseminate after exposure and can access target cells throughout the FRT, with an apparent preference for infection in squamous vaginal and ectocervical mucosa. JRFL enveloped virions infect diverse CD4 expressing cell types, with T cells resident throughout the FRT representing the primary target. These findings establish a new perspective that the entire FRT is susceptible and virus can reach as far as the ovary and local draining lymph nodes. Based on these findings, it is essential that protective mechanisms for prevention of HIV acquisition must be present at protective levels throughout the entire FRT to provide complete protection.
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stieh
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Danijela
authors.initials: D
authors.lastname: Maric
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Kelley
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Meegan R
authors.initials: MR
authors.lastname: Anderson
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Holly Z
authors.initials: HZ
authors.lastname: Hattaway
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Beilfuss
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Katharina B
authors.initials: KB
authors.lastname: Rothwangl
authors.affiliation: Tulane National Primate Research Center, Division of Comparative Pathology, Covington, Louisiana, United States of America.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Cellular and Molecular Biology, Chicago, Illinois, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
mesh_terms: D000818:Animals; D002460:Cell Line; D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000821:virology*; D008198:Lymph Nodes / Q000821:virology*; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000821:virology*; D051381:Rats; D015302:Simian Immunodeficiency Virus; D014621:Vagina / Q000821:virology*