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Journal of Virology, November 2007, p. 12458-12464, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00326-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interactions between Human Immunodeficiency Virus Type 1 and Vaccinia Virus in Human Lymphoid Tissue Ex Vivo{triangledown}

Christophe Vanpouille,1,2* Angélique Biancotto,1 Andrea Lisco,1 and Beda Brichacek1,2

Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 20892,1 The George Washington University Medical Center, Washington, DC 200372

Received 13 February 2007/ Accepted 24 August 2007

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 R5SF162 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.

* Corresponding author. Mailing address: 10 Center Drive (NIH), Bldg. 10, Room 9D58, Bethesda, MD 20892. Phone: (301) 594-0826. Fax: (301) 480-0857. E-mail: vanpouic{at}mail.nih.gov

{triangledown} Published ahead of print on 5 September 2007.

Journal of Virology, November 2007, p. 12458-12464, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00326-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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