tetano
Editor, Senior Moderator
J Virol
. 2021 Jul 28;JVI0067221.
doi: 10.1128/JVI.00672-21. Online ahead of print.
Phosphorylation of JIP4 at S730 presents anti-viral properties against influenza A virus infection
Juliana Del Sarto[SUP] 1 2 [/SUP], Vanessa Gerlt[SUP] 1 [/SUP], Marcel Edgar Friedrich[SUP] 1 [/SUP], Darisuren Anhlan[SUP] 1 [/SUP], Viktor Wixler[SUP] 1 [/SUP], Mauro Martins Teixeira[SUP] 2 [/SUP], Yvonne Boergeling[SUP] 1 [/SUP], Stephan Ludwig[SUP] 1 [/SUP]
Affiliations
Abstract
Influenza A virus (IAV) is the causative agent of flu disease that results in annual epidemics and occasional pandemics. IAV alters several signaling pathways of the cellular host response in order to promote its replication. Therefore, some of these pathways can serve as targets for novel anti-viral agents. Here, we show that c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) 4 is dynamically phosphorylated in IAV infection. Lack of JIP4 resulted in higher virus titers with significant differences in viral protein and mRNA accumulation as early as within the first replication cycle. In accordance, decreased IAV titers and protein accumulation was observed during overexpression of JIP4. Strikingly, the anti-viral function of JIP4 does neither originate from a modulation of JNK or p38 MAPK pathways, nor from altered expression of interferons or interferon-stimulated genes, but rather from a direct reduction of viral polymerase activity. Furthermore, interference of JIP4 with IAV replication seems to be linked to phosphorylation of the serine at position 730 that is sufficient to impede with the viral polymerase. Collectively, we provide evidence that JIP4, a host protein modulated in IAV infection, exhibits anti-viral properties that are dynamically controlled by its phosphorylation at S730. Importance Influenza A virus (IAV) infection is a world health concern and current treatment options encounter high rates of resistance. Our group investigates host pathways modified in IAV infection as promising new targets. Host protein JIP4 is dynamically phosphorylated in IAV infection. JIP4 absence resulted in higher virus titers, viral protein and mRNA accumulation within the first replication cycle. Accordingly, decreased IAV titers and protein accumulation was observed during JIP4 overexpression. Strikingly, the anti-viral function of JIP4 does neither originate from a modulation of JNK or p38 MAPK pathways, nor from altered expression of interferons or interferon-stimulated genes, but rather from a reduction in viral polymerase activity. Interference of JIP4 with IAV replication is linked to phosphorylation of serine 730. We provide evidence that JIP4, a host protein modulated in IAV infection, exhibits anti-viral properties that are dynamically controlled by its phosphorylation at S730.
. 2021 Jul 28;JVI0067221.
doi: 10.1128/JVI.00672-21. Online ahead of print.
Phosphorylation of JIP4 at S730 presents anti-viral properties against influenza A virus infection
Juliana Del Sarto[SUP] 1 2 [/SUP], Vanessa Gerlt[SUP] 1 [/SUP], Marcel Edgar Friedrich[SUP] 1 [/SUP], Darisuren Anhlan[SUP] 1 [/SUP], Viktor Wixler[SUP] 1 [/SUP], Mauro Martins Teixeira[SUP] 2 [/SUP], Yvonne Boergeling[SUP] 1 [/SUP], Stephan Ludwig[SUP] 1 [/SUP]
Affiliations
- PMID: 34319782
- DOI: 10.1128/JVI.00672-21
Abstract
Influenza A virus (IAV) is the causative agent of flu disease that results in annual epidemics and occasional pandemics. IAV alters several signaling pathways of the cellular host response in order to promote its replication. Therefore, some of these pathways can serve as targets for novel anti-viral agents. Here, we show that c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) 4 is dynamically phosphorylated in IAV infection. Lack of JIP4 resulted in higher virus titers with significant differences in viral protein and mRNA accumulation as early as within the first replication cycle. In accordance, decreased IAV titers and protein accumulation was observed during overexpression of JIP4. Strikingly, the anti-viral function of JIP4 does neither originate from a modulation of JNK or p38 MAPK pathways, nor from altered expression of interferons or interferon-stimulated genes, but rather from a direct reduction of viral polymerase activity. Furthermore, interference of JIP4 with IAV replication seems to be linked to phosphorylation of the serine at position 730 that is sufficient to impede with the viral polymerase. Collectively, we provide evidence that JIP4, a host protein modulated in IAV infection, exhibits anti-viral properties that are dynamically controlled by its phosphorylation at S730. Importance Influenza A virus (IAV) infection is a world health concern and current treatment options encounter high rates of resistance. Our group investigates host pathways modified in IAV infection as promising new targets. Host protein JIP4 is dynamically phosphorylated in IAV infection. JIP4 absence resulted in higher virus titers, viral protein and mRNA accumulation within the first replication cycle. Accordingly, decreased IAV titers and protein accumulation was observed during JIP4 overexpression. Strikingly, the anti-viral function of JIP4 does neither originate from a modulation of JNK or p38 MAPK pathways, nor from altered expression of interferons or interferon-stimulated genes, but rather from a reduction in viral polymerase activity. Interference of JIP4 with IAV replication is linked to phosphorylation of serine 730. We provide evidence that JIP4, a host protein modulated in IAV infection, exhibits anti-viral properties that are dynamically controlled by its phosphorylation at S730.