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Open Access Highly Accessed Research article

Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with Vaccinia Virus

Raymond S Weinstein1*, Michael M Weinstein2, Kenneth Alibek3, Michael I Bukrinsky4 and Beda Brichacek56

Author Affiliations

1 Biodefense Program, Department of Public and International Affairs, George Mason University, 10900 University Blvd., MS 1H8, Manassas, VA 20110, USA

2 Department of Human Genetics, University of California at Los Angeles, Gonda (Goldschmied) Neuroscience and Genetics Research Center, 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095, USA

3 AFG Biosolutions, 9119 Gaither Rd., Gaithersberg, MD 20877, USA

4 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Ross Hall, Suite 734, 2300 Eye St., N. W., Washington, DC 20037, USA

5 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Ross Hall, Suite 734, 2300 Eye St., N. W., Washington, DC 20037, USA.

6 Current address: National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

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BMC Immunology 2010, 11:23  doi:10.1186/1471-2172-11-23

Published: 18 May 2010

Abstract

Background

At present, the relatively sudden appearance and explosive spread of HIV throughout Africa and around the world beginning in the 1950s has never been adequately explained. Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization, we undertook a comparison of HIV-1 susceptibility in the peripheral blood mononuclear cells from subjects immunized with the vaccinia virus to those from vaccinia naive donors.

Results

Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1α, MIP-1β and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge.

Discussion

Since primary HIV-1 infections are caused almost exclusively by the CCR5-tropic HIV-1 strains, our results suggest that prior immunization with vaccinia virus might provide an individual with some degree of protection to subsequent HIV infection and/or progression. The duration of such protection remains to be determined. A differential elaboration of MIP-1α, MIP-1β and RANTES between vaccinated and unvaccinated subjects, following infection, does not appear to be a mechanism in the noted protection.