In the nine countries in southern Africa most affected by HIV-1, prevalence among these young women was on average about three times higher than among men of the same age [2]. cells. HeLa cells were exposed to progeny computer virus from CEMx174 cells infected with HIV alone (HIV-1), XMRV alone (XMRV) or co-infected with both (HIV/XMRV). Supernatant from uninfected CEMx174 cells (mock) was used as a control. Immunofluorescence staining and circulation cytometry analysis were then performed with FITC-anti-HIV-1 Gag MAb. HeLa cells were also exposed to infected by the progeny computer virus from HIV/XMRV co-infected cells in presence of AZT (second panel). (B) The neutralizing activity of 2F5 antibody against HIV-1 was confirmed by exposing TZM-bl cells to HIV-1 in the presence of dilutions of the antibody. Contamination was assessed after 2 days by measuring luciferase activity as explained in Materials and Methods.(TIF) pone.0101367.s002.tif (887K) GUID:?D6097C6F-2883-4707-B4BD-83CA8C42C2DA Physique S3: Isolation Trimethadione and characterization of main cervical and vaginal epithelial cells. (A) Representative image to show epithelial cells migrating from tissue explants after 5 days Trimethadione of culture. Endocervix (B) and vagina (C) derived epithelial cells created monolayers after 7 days of culture. D, E, F, G: The epithelial cells from endocervix (D, F) or vagina and ectocervix (E, G respectively) were subjected to immunofluorescence staining for the indicated protein as explained in Materials and Methods.(TIF) pone.0101367.s003.tif (3.0M) GUID:?B5F45634-54BA-42C6-AC30-880D7D5F89F0 Figure S4: Visualization of R5 strain HIV-1Bal infection of main endocervical epithelial cells. Dual immunofluorescence staining with FITC-anti-HIV-1 Gag and anti-CK19 Mabs was performed in main endocervical epithelial cells that were exposed to progeny computer virus from infected CEMx174 cells. The input viruses used to infect CEMx174 cells are indicated (HIV?=?HIV alone; XMRV?=?XMRV alone; HIV/XMRV?=?co-infected with both). Epithelial cells exposed to progeny computer virus in presence of AZT or anti-MLV polyclonal sera diluted 1300 are shown as indicated (B, left two columns). HIV-1 Gag is usually shown as green and CK19 as reddish. Green fluorescence merged to the corresponding bright field is usually shown in (A).(TIF) pone.0101367.s004.tif (2.5M) GUID:?E07397FB-15DA-493B-8392-9F4C193187BA 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 Trimethadione exceeds 20%. The devastating spread of the computer virus in young women in these countries appears disproportional to overall risk of contamination. 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 contamination 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 computer virus (XMRV), progeny HIV-1 particles are produced capable of infecting main vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 contamination. EMR2 Trimethadione Infection of main genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that contamination 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 computer 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 computer virus. Introduction The HIV/AIDS pandemic is primarily sustained by heterosexual transmission of HIV-1 and more than half of all new infections occur in young women. The prevalence of HIV-1 in some regions of Africa has exceeded 20% [1] and in sub-Saharan Africa, females constitute 75% of infected individuals between the ages of 15 and 24. In the nine countries in southern Africa most affected by HIV-1, prevalence among these young women was on average about three occasions higher than among men of the same age [2]. The computer virus is distributing among women at a rate that cannot be explained by.