title: Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1: possible implications for sexual transmission of HIV-1.
abstract: The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call "natural pseudotyping," expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus.
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California Davis, Davis, California, United States of America.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California Davis, Davis, California, United States of America.
authors.forename: Alvin
authors.initials: A
authors.lastname: George
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California Davis, Davis, California, United States of America.
authors.forename: Franklin
authors.initials: F
authors.lastname: Nouvet
authors.affiliation: Department of Obstetrics and Gynecology, University of California Davis, Davis, California, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sweet
authors.affiliation: Department of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Nkiruka
authors.initials: N
authors.lastname: Emeagwali
authors.affiliation: Department of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Harry E
authors.initials: HE
authors.lastname: Taylor
authors.affiliation: Department of Microbiology and Immunology, Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, Tennessee, United States of America.
authors.forename: Glenn
authors.initials: G
authors.lastname: Simmons
authors.affiliation: Department of Molecular and Cellular Biology, College of Biological Sciences, University of California Davis, Davis, California, United States of America.
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology*; D003075:Coitus; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D014621:Vagina / Q000166:cytology*; D056189:Viral Tropism; D014779:Virus Replication; D058008:Xenotropic murine leukemia virus-related virus / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing