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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1305-1313.
Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2004-12-4899.
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Submitted December 29, 2004
Accepted April 12, 2005
Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses
Silvia Peretti, Andrew Shaw, James Blanchard, Rudolf Bohm, Gavin Morrow, Jeffrey D Lifson, Agegnehu Gettie, and Melissa Pope*
Center for Biomedical Research, Population Council, New York, NY, USA
Tulane National Primate Research Center, Tulane University, Covington, LA, USA
AIDS Vaccine Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD, USA
Aaron Diamond AIDS Research Center, New York, NY, USA
* Corresponding author; email: mpope{at}popcouncil.org.
Herpes Simplex Viruses (HSV) infect human and murine dendritic cells (DCs) and interfere with their immunostimulatory functions in culture. HSV-2 infection increases human immunodeficiency virus (HIV) spread in patients and DCs also promote HIV infection. We have studied these topics in rhesus macaque monocyte-derived DCs (moDCs), to set the stage for future studies of these issues in animals. We provide the first evidence that macaque DCs become infected by HSV-2. Structural viral proteins (ICP5, gD, envelope) were detected in the cell periphery and a functional protein (ICP8) was predominantly found in the nucleus after infection. Infectious HSV-2 induced apoptotic death, decreased expression of HLA-DR, CD40, CD80, CD83, and CD86, and increased release of IL-6, TNF- , MIP-1 (CCL3), and RANTES (CCL5), but not IL-12 or IFN- by macaque DCs. This coincided with HSV-2-infected DCs stimulating weak T cell responses, including impaired SIV-specific responses. Comparable HSV-2 protein expression, DC apoptosis, as well as membrane immunophenotype and functional modifications were observed in HSV-2-exposed human moDCs. Such HSV-2-induced modifications of macaque and human DCs could augment DC-driven immunodeficiency virus infection. This work affords the basis for future macaque studies to explore how HSV-2 impacts the efficacy of strategies being developed to prevent HIV transmission.

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