Rift Valley fever virus inhibits a pro-inflammatory response in experimentally infected human monocyte derived macrophages and a pro-inflammatory cytokine response may be associated with patient survival during natural infection.
Rift Valley fever virus (RVFV) causes significant morbidity and mortality in humans and livestock throughout Africa and the Middle East. The clinical disease ranges from mild febrile illness, to hepatitis, retinitis, encephalitis and fatal hemorrhagic fever. RVFV NSs protein has previously been shown to interfere in vitro with the interferon response, and RVFV lacking the NSs protein is attenuated in several animal models. Monocytes and macrophages are key players in the innate immune response via expression of various cytokines and chemokines. Here we demonstrate that wild-type RVFV infection of human monocyte-derived macrophages leads to a productive infection and inhibition of the innate immune response via decreased expression of IFN-α2, IFN-β and TNF-α. Using a recombinant virus lacking the NSs protein, we show that this effect is mediated by the viral NSs protein. Finally, analysis of RVF patient samples demonstrated an association between a pro-inflammatory cytokine response and patient survival.
Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control, MS G14, Atlanta, GA 30333, USA. gsz5@cdc.gov
Anita K
AK
McElroy
Stuart T
ST
Nichol
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012295:Rift Valley Fever / Q000276:immunology* / Q000401:mortality / Q000821:virology; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000172:deficiency / Q000235:genetics*
D016207:Cytokines; D016898:Interferon-alpha; C423923:NSs protein, Bunyamwera bunyavirus; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta