A novel mechanism of HIV transcytosis and infection

Gupta et al. Retrovirology 2012, 9(Suppl 2):P206 http://www.retrovirology.com/content/9/S2/P206 POSTER PRESENTATION Open Access A novel mechanism of HIV transcytosis and infection S Gupta * , JC Becerra, DN Forthal From AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 2012 Background Female genital tract mucosae are bathed in acidic secre- tions, which, in the case of HIV-1 infected women, likely contain virus coated with antibody. Thus, uninfected male sexual partners are often exposed to an acidic milieu con- taining virus in the form of immune complexes. We inves- tigated the impact of low pH and antibody on transcytosis, a potentially critical mechanism by which HIV-1 passes through genital tract epithelia to infect susceptible target cells. Methods HIV-1 was incubated with Env-specific monoclonal and polyclonal antibodies at pH 6.0 or pH 7.4 and exposed to the apical surface of tight junction-forming human endometrial carcinoma (HEC-1) cells in transwell plates. The quantity and infectivity of transcytosed virus was measured by RT-PCR and infection of TZMbl cells, respectively. Results We found that the combination of acidic pH and Env-spe- cific antibody augmented transcytosis as much as 30-fold compared with Env-specific antibody at neutral pH or compared with non-specific antibody or no antibody at neutral or acidic pH. The pH and antibody dependence of enhanced transcytosis was blocked by antibody specific for the Fc neonatal receptor (FcRn) or by treatment with bafi- lomycin A1 (which inhibits acidification of endosomes). Non-neutralizing antibodies resulted in a lower quantity of total transcytosed virus, measured by RT-PCR, than did neutralizing antibodies. However, the ratio of total to infectious virus was much higher for neutralizing antibo- dies, indicating that neutralizing antibodies efficiently allow transcytosis while blocking infectivity of the transcytosed virus; the non-neutralizing antibodies facili- tate transcytosis (although to a lesser degree than the neu- tralizing antibodies) without blocking infectivity. Conclusion These results demonstrate that acidity and Env-specific antibody greatly enhance transcytosis of virus across mucosal epithelial cells via FcRn. Since male penile and urethral tissues express FcRn, our results suggest a novel mechanism by which antibody, and in particular, non- neutralizing antibody, might facilitate female-to-male transmission following sexual exposure. Published: 13 September 2012 doi:10.1186/1742-4690-9-S2-P206 Cite this article as: Gupta et al.: A novel mechanism of HIV transcytosis and infection. Retrovirology 2012 9(Suppl 2):P206. Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color figure charges • Immediate publication on acceptance • Inclusion in PubMed, CAS, Scopus and Google Scholar • Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit University of California Irvine, Irvine, CA, USA © 2012 Gupta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.