Interactions between human immunodeficiency virus type 1 and vaccinia virus in human lymphoid tissue ex vivo

J Virol. 2007 Nov;81(22):12458-64. doi: 10.1128/JVI.00326-07. Epub 2007 Sep 5.

Abstract

Vaccinia virus (VACV) has been attracting attention recently not only as a vector for various vaccines but also as an immunization tool against smallpox because of its potential use as a bioterrorism agent. It has become evident that in spite of a long history of studies of VACV, its tissue pathogenesis remains to be fully understood. Here, we investigated the pathogenesis of VACV and its interactions with human immunodeficiency virus type 1 (HIV-1) in the context of human lymphoid tissues. We found that ex vivo-cultured tonsillar tissue supports productive infection by the New York City Board of Health strain, the VACV strain of the Dryvax vaccine. VACV readily infected both T and non-T (B) lymphocytes and depleted cells of both of these subsets equally over a 12-day period postinfection. Among T lymphocytes, CD8(+) cells are preferentially depleted in accordance with their preferential infection: the probability that a CD8(+) T cell will be productively infected is almost six times higher than for a CD4(+) T cell. T cells expressing CCR5 and the activation markers CD25, CD38, and HLA-DR are other major targets for infection by VACV in lymphoid tissue. As a consequence, VACV predominantly inhibits the replication of the R5(SF162) phenotype of HIV-1 in coinfected tissues, as R5-tropic HIV-1 requires activated CCR5(+) CD4(+) cells for productive infection. Human lymphoid tissue infected ex vivo by VACV can be used to investigate interactions of VACV with other viruses, in particular HIV-1, and to evaluate various VACV vectors for the purpose of recombinant vaccine development.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Chemokines, CXC / metabolism
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / virology*
  • Palatine Tonsil / virology
  • Receptors, CCR5 / analysis
  • Receptors, CCR5 / metabolism
  • T-Lymphocytes / immunology
  • Vaccinia virus / pathogenicity*
  • Vaccinia virus / physiology
  • Virus Replication*

Substances

  • Chemokines, CXC
  • Receptors, CCR5