Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1: Possible implications for sexual transmission of HIV-1

Yuyang Tang, Alvin George, Franklin Nouvet, Stephanie Sweet, Nkiruka Emeagwali, Harry E. Taylor, Glenn Simmons, James E K Hildreth

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere101367
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 10 2014
Externally publishedYes

Fingerprint

Human immunodeficiency virus 1
Viruses
genitalia
HIV-1
epithelial cells
Epithelial Cells
Gammaretrovirus
Xenotropic murine leukemia virus-related virus
Infection
viruses
infection
glycoproteins
Glycoproteins
tropisms
Tropism
HIV Infections
Southern Africa
Coitus
virus transmission
female genitalia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1 : Possible implications for sexual transmission of HIV-1. / Tang, Yuyang; George, Alvin; Nouvet, Franklin; Sweet, Stephanie; Emeagwali, Nkiruka; Taylor, Harry E.; Simmons, Glenn; Hildreth, James E K.

In: PLoS One, Vol. 9, No. 7, e101367, 10.07.2014.

Research output: Contribution to journalArticle

Tang, Yuyang ; George, Alvin ; Nouvet, Franklin ; Sweet, Stephanie ; Emeagwali, Nkiruka ; Taylor, Harry E. ; Simmons, Glenn ; Hildreth, James E K. / Infection of female primary lower genital tract epithelial cells after natural pseudotyping of HIV-1 : Possible implications for sexual transmission of HIV-1. In: PLoS One. 2014 ; Vol. 9, No. 7.
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