title: Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions.
abstract: Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.
authors.affiliation: Division of HIV/AIDS Prevention, Surveillance, and Epidemiology, National Center for HIV, STD, and TB Prevention, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. tve1@cdc.gov
authors.forename: T V
authors.initials: TV
authors.lastname: Ellerbrock
authors.forename: J L
authors.initials: JL
authors.lastname: Lennox
authors.forename: K A
authors.initials: KA
authors.lastname: Clancy
authors.forename: R F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: T C
authors.initials: TC
authors.lastname: Wright
authors.forename: M
authors.initials: M
authors.lastname: Pratt-Palmore
authors.forename: T
authors.initials: T
authors.lastname: Evans-Strickfaden
authors.forename: C
authors.initials: C
authors.lastname: Schnell
authors.forename: R
authors.initials: R
authors.lastname: Pai
authors.forename: L J
authors.initials: LJ
authors.lastname: Conley
authors.forename: E E
authors.initials: EE
authors.lastname: Parrish-Kohler
authors.forename: T J
authors.initials: TJ
authors.lastname: Bush
authors.forename: K
authors.initials: K
authors.lastname: Tatti
authors.forename: C E
authors.initials: CE
authors.lastname: Hart
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009093:Mucus / Q000821:virology; D010641:Phenotype; D011446:Prospective Studies; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014621:Vagina / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D012333:RNA, Messenger