title: Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells modify innate and adaptive responses.
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.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY 10021. mpope@popcouncil.org.
authors.forename: Silvia
authors.initials: S
authors.lastname: Peretti
authors.forename: Andrew
authors.initials: A
authors.lastname: Shaw
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bohm
authors.forename: Gavin
authors.initials: G
authors.lastname: Morrow
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Melissa
authors.initials: M
authors.lastname: Pope
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015658:HIV Infections / Q000209:etiology; D006684:HLA-DR Antigens / Q000032:analysis; D006558:Herpes Genitalis / Q000150:complications / Q000276:immunology*; D018258:Herpesvirus 2, Human; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008253:Macaca mulatta; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens