Failure to detect active virus replication in mast cells at various tissue sites of HIV patients by immunohistochemistry

Int J Biol Sci. 2009 Sep 22;5(6):603-10. doi: 10.7150/ijbs.5.603.

Abstract

A recent report postulated that the mast cell population is a significant reservoir for persistent HIV infection. Our study attempted to validate this hypothesis by quantitatively comparing the distribution of mast cells and cells expressing the HIV protein p24 in HIV infected patients. Consecutive sections of paraffin-embedded human tissues from various tissue sites were subjected to immunohistochemistry with monoclonal antibodies to mast cell tryptase, viral protein p24, and other molecules. The sub-cellular distribution of these molecules was examined, to determine whether immunoreactivities to these molecules would be co-localized within the same cells. Our study revealed that, in two immediate adjacent sections immunostained for mast cell tryptase and p24, respectively, all or nearly all tryptase and p24 expressing cells were distributed at different areas. In the single section double immunostained for mast cell tryptase and p24, 5 (1.1%) of 460 large p24 expressing cell clusters encountered showed a single or few mast cells within or adjacent to p24 expressing cell clusters, but no distinct co-localization of these two proteins was observed. Similarly, no distinct co-localization was observed in any of over 500 isolated individual mast cells and p24 expressing cells. In contrast, macrophages were consistently intermixed with or adjacent to p24 expressing cells, and p24 immunostaining were seen in the cytoplasm of a subset of macrophages. These findings suggest that tissue mast cells do not show evidence for active virus replication by the techniques employed.

Keywords: HIV protein p24; HIV reservoir; macrophages; mast cells; persistent HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Count
  • Cervix Uteri / virology
  • Cytoplasm / metabolism
  • Cytoplasm / virology
  • Female
  • Gastrointestinal Tract / virology
  • HIV / physiology*
  • HIV Core Protein p24 / metabolism*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / virology
  • Macrophages / physiology
  • Mast Cells / physiology
  • Mast Cells / virology*
  • Nasopharynx / virology
  • Parotid Gland / virology
  • Tryptases / metabolism
  • Virus Replication*

Substances

  • HIV Core Protein p24
  • Tryptases