Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses
Peretti,Silvia; Shaw,Andrew; Blanchard,James; Bohm,Rudolf; Morrow,Gavin; Lifson,Jeffrey D.; Gettie,Agegnehu; Pope,Melissa
Blood 106(4): 1305-1313
Publication date: 2005
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-α, MIP-1α (CCL3), and RANTES (CCL5), but not IL-12 or IFN-α 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.