Scientific Publications by FDA Staff

J Steroid Biochem Mol Biol 2013 Nov;138:63-71

Effect of sex steroid hormones on replication and transmission of major HIV subtypes.

Ragupathy V, Devadas K, Tang S, Wood O, Lee S, Dastyer A, Wang X, Dayton A, Hewlett I

BACKGROUND: HIV epidemic is expanding worldwide with an increasing number of distinct viral subtypes and circulating recombinant forms (CRFs). Out of 34 million adults living with HIV and AIDS, women account for one half of all HIV-1 infections worldwide. These gender differences in HIV pathogenesis may be attributed to sex hormones. Little is known about the role of sex hormone effects on HIV Subtypes pathogenesis. The aim of our study was to determine sex hormone effects on human immunodeficiency virus (HIV) subtypes replication and transmissibility. METHODS: Peripheral blood mononuclear cells (PBMC) from male and female donors were infected with HIV subtypes A-D and CRF02_AG, CRF01_AE, MN (lab adapted), Group-O, Group-N and HIV-2 at a concentration of 5ng/ml of p24 or p27. Virus production was evaluated by measuring p24 and p27 levels in culture supernatants. Similar experiments were carried out in the presence of physiological concentrations of sex steroid hormones. R5/X4 expressions measured by flow cytometry and transmissibility was evaluated by transfer of HIV from primary dendritic cells (DC) to autologous donor PBMC's. RESULTS: Our results from primary Peripheral Blood Mononuclear Cells (PBMC) and Monocyte Derived Dendritic Cells (MDDC) from male and female donors indicate in the absence of physiological concentrations of hormone treatment virus production was observed in three clusters high replicating virus (Subtype B and C), moderate replicative virus (Subtype A, D, CRF_01 AE, Group_N) and least replicative virus (strain MN). However, dose of a sex steroid hormone treatment influences HIV replication and transmission kinetics in PBMC, DCs and cell lines. Such effect were inconsistent between donors and HIV subtypes. Sex hormone effect on HIV entry receptors (CCR5/CXCR4) did not correlate with virus production. CONCLUSIONS: Subtypes B and C showed higher replication in PBMC from males and females and were transmitted more efficiently through dendritic cells to male and female PBMC compared with other HIV-1 subtypes, HIV-1 Group O and HIV-2. These findings are consistent with increased worldwide prevalence of subtype B and C compared to other subtypes. Sex steroid hormones had variable effect on replication or transmission of different subtypes. These findings suggest that subtype, gender and sex hormones may play a crucial role in the replication and transmission of HIV.