Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques

PLoS Pathog. 2013;9(12):e1003810. doi: 10.1371/journal.ppat.1003810. Epub 2013 Dec 12.

Abstract

The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • DNA, Viral / analysis
  • Disease Models, Animal
  • Macaca fascicularis
  • Macrophages / immunology
  • Macrophages / virology*
  • Male
  • Phenotype
  • Semen / cytology
  • Semen / immunology*
  • Semen / virology*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus* / physiology
  • Virus Shedding

Substances

  • DNA, Viral

Grant support

This study was supported by the Fond de Dotation Pierre Bergé (SIDACTION, France), the Combined Highly Active Anti-Retroviral Microbicides (CHAARM, EU FP7 grand N° 242135) European network, and the Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS, France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.