Interactions between human immunodeficiency virus type 1 and vaccinia virus in human lymphoid tissue ex vivo.
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.
Vanpouille
Christophe
C
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. vanpouic@mail.nih.gov
Biancotto
Angélique
A
Lisco
Andrea
A
Brichacek
Beda
B
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019743:Chemokines, CXC / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology*; D014066:Palatine Tonsil / Q000821:virology; D019713:Receptors, CCR5 / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014616:Vaccinia virus / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication