Estradiol Reduces Susceptibility of CD4+ T Cells and Macrophages to HIV-Infection

Authors

Marta Rodriguez-Garcia, Dartmouth College
Nabanita Biswas, Dartmouth College
Mickey V. Patel, Dartmouth College
Fiona D. Barr, Dartmouth CollegeFollow
Sarah G. Christ, Dartmouth College
Chrsitina Ochsenbauer, University of Alabama, Birmingham
John V. Fahey, Dartmouth CollegeFollow
Charles R. Wira, Dartmouth College

Document Type

Article

Publication Date

4-17-2013

Publication Title

PloS One

Department

Geisel School of Medicine

Abstract

The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-b-estradiol (E₂) and ethinyl estradiol (EE) in HIV-infection of CD4⁺ T-cells and macrophages. Purified CD4⁺ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4⁺ T-cells and macrophages with E₂ prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E₂ 2h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E₂ and had no effect on CD4⁺ T-cell infection. Reduction of HIV-infection induced by E₂ in CD4⁺ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E₂. In macrophages, despite the lack of an effect of on CCR5 expression, E₂ –treatment reduced viral entry 2 h after challenge and increased MIP-1 b secretion. These results demonstrate the direct effect of E₂ on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms.

DOI

10.1371/journal.pone.0062069

Original Citation

Rodriguez-Garcia M, Biswas N, Patel MV, Barr FD, Crist SG, Ochsenbauer C, Fahey JV, Wira CR. Estradiol reduces susceptibility of CD4+ T cells and macrophages to HIV-infection. PLoS One. 2013 Apr 17;8(4):e62069. doi: 10.1371/journal.pone.0062069. PMID: 23614015; PMCID: PMC3629151.

Dartmouth Digital Commons Citation

Rodriguez-Garcia, Marta; Biswas, Nabanita; Patel, Mickey V.; Barr, Fiona D.; Christ, Sarah G.; Ochsenbauer, Chrsitina; Fahey, John V.; and Wira, Charles R., "Estradiol Reduces Susceptibility of CD4+ T Cells and Macrophages to HIV-Infection" (2013). Dartmouth Scholarship. 2689.
https://digitalcommons.dartmouth.edu/facoa/2689