title: Cytokine response in mouse bone marrow derived macrophages after infection with pathogenic and non-pathogenic Rift Valley fever virus.
abstract: Rift Valley fever virus (RVFV) is the most pathogenic member of the genus Phlebovirus within the family Bunyaviridae, and can cause severe disease in humans and livestock. Until recently, limited information has been published on the cellular host response elicited by RVFV, particularly in macrophages and dendritic cells, which play critical roles in stimulating adaptive and innate immune responses to viral infection. In an effort to define the initial response of host immunomodulatory cells to infection, primary mouse bone marrow derived macrophages (BMDM) were infected with the pathogenic RVFV strain ZH501, or attenuated strains MP-12 or MP-12 based Clone13 type (rMP12-C13 type), and cytokine secretion profiles examined. The secretion of T helper (Th)1-associated antiviral cytokines, chemokines and various interleukins increased rapidly after infection with the attenuated rMP12-C13 type RVFV, which lacks a functional NSs virulence gene. In comparison, infection with live-attenuated MP-12 encoding a functional NSs gene appeared to cause a delayed immune response, while pathogenic ZH501 ablates the immune response almost entirely. These data demonstrate that NSs can inhibit components of the BMDM antiviral response and supports previous work indicating that NSs can specifically regulate the type I interferon response in macrophages. Furthermore, our data demonstrate that genetic differences between ZH501 and MP-12 reduce the ability of MP-12 to inhibit antiviral signalling and subsequently reduce virulence in BMDM, demonstrating that viral components other than NSs play a critical role in regulating the host response to RVFV infection.
authors.affiliation: 1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Roberts
authors.affiliation: 1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Terence E
authors.initials: TE
authors.lastname: Hill
authors.affiliation: 2Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Davis
authors.affiliation: 6Integrated Research Facility, National Institute of Allergy and Infectious Disease, National Institutes of Health, Frederick, MD, USA.|5Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, USA.|1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.|2Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|4Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|3Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
authors.affiliation: 3Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.|4Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|1Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.|5Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008810:Mice, Inbred C57BL; D012296:Rift Valley fever virus / Q000254:growth & development / Q000276:immunology*; D014774:Virulence
chemical_list: D016207:Cytokines