Abstract
Humans and avian species are prone to influenza viral infection, which may cause serious clinical consequences. Many studies have documented the critical role of host factors in the influenza virus life cycle based on human models, but knowledge about their roles in birds is very limited. In this study, using immunoprecipitation coupled with mass spectrometry, a total of 72 potential interacting proteins of influenza nucleoprotein (NP) were identified in DF-1 cells. Among these proteins, avian chaperonin containing TCP1 subunit 5 (CCT5) was demonstrated to interact with influenza A virus (IAV) NP directly, as well as polymerase basic protein 1 (PB1) and polymerase basic protein 2 (PB2) but not with polymerase acidic protein (PA). Further investigation showed that viral infection profoundly elevated the expression level of cellular CCT5, whose expression, in turn, promoted the nuclear export of NP, as well as viral polymerase activity, thereby facilitating the replication of IAV. The obtained results suggested an important role of avian CCT5 in supporting influenza virus replication, which may serve as an anti-influenza target.
Highlights
Influenza virus, a negative-sense RNA virus with a genome consisting of eight gene segments, is a highly dangerous pathogen circulated in both humans and animals around the world (Lamb and Choppin, 1983; Luo et al, 2018)
Viral RNP complex, which consists of a single-stranded negative-sense genomic RNA, multiple copies of the viral nucleoprotein (NP), and an RNA polymerase complex composed of polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and
To explore the potential host proteins that interact with influenza A virus (IAV) nucleoprotein NP, we performed IP assay in DF-1 cells transfected with a plasmid expressing HA-labeled H5N6 influenza NP (HA-NP)
Summary
A negative-sense RNA virus with a genome consisting of eight gene segments, is a highly dangerous pathogen circulated in both humans and animals around the world (Lamb and Choppin, 1983; Luo et al, 2018). The influenza virus needs to hijack the host components to complete the synthesis of viral RNA (vRNA) and proteins (Herz et al, 1981; Jackson et al, 1982; O’Neill et al, 1995). Viral RNP (vRNP) complex, which consists of a single-stranded negative-sense genomic RNA, multiple copies of the viral nucleoprotein (NP), and an RNA polymerase complex composed of polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and CCT5 Supports IAV Replication polymerase acidic protein (PA), is the basic unit of influenza A virus (IAV) transcription and replication (Jennings et al, 1983; Hsu et al, 1987; Klumpp et al, 1997). Studies on the involvement of avian host factors in interacting with influenza NP are limited
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