title: Effect of sex steroid hormones on replication and transmission of major HIV subtypes.
abstract: BACKGROUND
  The 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 replication and transmissibility of HIV subtypes.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) and monocyte derived dendritic cells (MDDC) 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.
  
  
  RESULTS
  Our results from primary PBMC and 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, CRF01_AE, Group_N) and least replicative virus (strain MN). However, dose of sex steroid hormone treatment influenced HIV replication and transmission kinetics in PBMC, DCs and cell lines. Such effects were inconsistent between donors and HIV subtypes. Sex hormone effects 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 DC 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.
authors.affiliation: Laboratory of Molecular Virology, Division of Emerging Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. Electronic address: Ragupathy.Viswanath@fda.hhs.gov.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Ragupathy
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Devadas
authors.forename: Shixing
authors.initials: S
authors.lastname: Tang
authors.forename: Owen
authors.initials: O
authors.lastname: Wood
authors.forename: Sherwin
authors.initials: S
authors.lastname: Lee
authors.forename: Armeta
authors.initials: A
authors.lastname: Dastyer
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Dayton
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D015658:HIV Infections / Q000378:metabolism / Q000635:transmission*; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C584933:CCR5 protein, human; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D019713:Receptors, CCR5; D013739:Testosterone; D011374:Progesterone
keywords: HIV; Replication kinetics; Sex hormones; Subtypes; Transmission kinetics