Viperin is highly induced in neutrophils and macrophages during acute and chronic lymphocytic choriomeningitis virus infection.
Although most cells are thought to respond to IFNs, there is limited information regarding specific cells that respond in vivo. Viperin is an IFN-induced antiviral protein and, therefore, is an excellent marker for IFN-responsive cells. In this study, we analyzed viperin expression in vivo during acute lymphocytic choriomeningitis virus Armstrong infection, which induces high levels of type I IFNs, and in persistently infected lymphocytic choriomeningitis virus carrier mice, which contain low levels of type I IFNs. Viperin was induced in lymphoid cells and dendritic cells (DCs) during acute infection and highly induced in neutrophils and macrophages. The expression kinetics in neutrophils, macrophages, and T and B cells paralleled IFN-alpha levels, but DCs expressed viperin with delayed kinetics. In carrier mice, viperin was expressed in neutrophils and macrophages but not in T and B cells or DCs. For acutely infected and carrier mice, viperin expression was IFN dependent, because treating type I IFNR knockout mice with IFN-gamma-neutralizing Abs inhibited viperin expression. Viperin localized to the endoplasmic reticulum and lipid droplet-like vesicles in neutrophils. These findings delineate the kinetics and cells responding to IFNs in vivo and suggest that the profile of IFN-responsive cells changes in chronic infections. Furthermore, these data suggest that viperin may contribute to the antimicrobial activity of neutrophils.
Hinson
Ella R
ER
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Joshi
Nikhil S
NS
Chen
Jonathan H
JH
Rahner
Christoph
C
Jung
Yong Woo
YW
Wang
Xiuyan
X
Kaech
Susan M
SM
Cresswell
Peter
P
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D007370:Interferon Type I / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D010587:Phagocytosis / Q000276:immunology; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D000090123:Viperin Protein
D007370:Interferon Type I; D011506:Proteins; D053633:Receptor, Interferon alpha-beta; C417529:Rsad2 protein, mouse; D000090123:Viperin Protein
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