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Blood. 2005 Aug 15;106(4):1305-13. Epub 2005 Apr 21.

Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses.

Author information

1
Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY 10021. mpope@popcouncil.org.

Abstract

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 [infected cell protein 5], glycoprotein D [gD], envelope) were detected in the cell periphery, and a functional protein (infected cell protein 8 [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 interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP-1alpha) (CCL3), and RANTES (regulated on activation normal T cells expressed and secreted) (CCL5) but not IL-12 or interferon-alpha (IFN-alpha) 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.

PMID:
15845898
PMCID:
PMC1895187
DOI:
10.1182/blood-2004-12-4899
[Indexed for MEDLINE]
Free PMC Article
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