title: Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent.
abstract: Because both HIV-1 virions and HIV-infected cells are present in the semen and cervical mucus of infected individuals, HIV-1 prevention strategies must consider both cell-free and cell-associated virus. Antibodies that target HIV-1 virions have been shown to prevent vaginal transmission of cell-free virus in macaques, but since cell-associated transmission has not been reliably demonstrated in this model system, no strategies to prevent such transmission have been tested. We have employed a mouse model in which SCID mice carry human peripheral blood leukocytes (HuPBLs). In these mice, vaginal transmission of cell-associated, but not cell-free, HIV-1 transmission occurs, mediated by transepithelial migration of HIV-infected cells. Topical application of beta-cyclodextrin (beta-CD), a cholesterol-sequestering agent that interferes with cell migration and budding of virus from lipid rafts, blocks transmission of cell-associated HIV-1. The HuPBL-SCID model of vaginal HIV-1 transmission should prove useful for investigating cell-associated HIV-1 transmucosal HIV-1 transmission, as well as for screening reagents for their potential efficacy in preventing sexual HIV-1 transmission.
authors.affiliation: Johns Hopkins School of Hygiene and Public Health, Department of Microbiology and Immunology, Johns Hopkins University, Baltimore, Maryland 21205, USA. kkhanna@jhsph.edu
authors.forename: Kristen V
authors.initials: KV
authors.lastname: Khanna
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Whaley
authors.forename: Larry
authors.initials: L
authors.lastname: Zeitlin
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Moench
authors.forename: Karim
authors.initials: K
authors.lastname: Mehrazar
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cone
authors.forename: Zhaohao
authors.initials: Z
authors.lastname: Liao
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Hoen
authors.forename: Leonard
authors.initials: L
authors.lastname: Shultz
authors.forename: Richard B
authors.initials: RB
authors.lastname: Markham
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000287:Administration, Topical; D000818:Animals; D002465:Cell Movement; D003505:Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004848:Epithelium; D005079:Excipients / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000637:transplantation / Q000821:virology; D008198:Lymph Nodes; D051379:Mice; D016513:Mice, SCID; D010529:Peritoneal Cavity; D011374:Progesterone / Q000494:pharmacology; D014621:Vagina / Q000821:virology*; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011374:Progesterone