Open AccessThe innate immunity of guinea pigs against highly pathogenic avian influenza virus infection
Author(s) -
Kun Zhang,
Wei Xu,
Zhaowei Zhang,
Jing Liu,
Jing Li,
Lei Sun,
Wenzhao Sun,
Peirong Jiao,
Xiaoyu Sang,
Zhiguang Ren,
Zhijun Yu,
Yuanguo Li,
Ninghan Feng,
Tiecheng Wang,
Hualei Wang,
Cuiling Wang,
Yongkun Zhao,
Xuemei Zhang,
Peter R. Wilker,
Wenjun Liu,
Ming Liao,
Hualan Chen,
Yuwei Gao,
Xianzhu Xia
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.16503
Subject(s) - influenza a virus subtype h5n1 , virology , innate immune system , biology , virulence , viral replication , guinea pig , influenza a virus , virus , viral shedding , immunity , immunology , microbiology and biotechnology , immune system , gene , biochemistry , endocrinology
H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.