FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4377011867> ?p ?o ?g. }

• W4377011867 abstract "Multiple mechanisms exist in a cell to cope with stress. Four independent stress-sensing kinases constitute the integrated stress response machinery of the mammalian cell, and they sense the stress signals and act by phosphorylating the eukaryotic initiation factor 2α (eIF2α) to arrest cellular translation. Eukaryotic initiation factor 2 alpha kinase 4 (eIF2AK4) is one of the four kinases and is activated under conditions of amino acid starvation, UV radiation, or RNA virus infection, resulting in shutdown of global translation. An earlier study in our laboratory constructed the protein interaction network of the hepatitis E virus (HEV) and identified eIF2AK4 as a host interaction partner of the genotype 1 (g1) HEV protease (PCP). Here, we report that PCP's association with the eIF2AK4 results in inhibition of self-association and concomitant loss of kinase activity of eIF2AK4. Site-directed mutagenesis of the 53rd phenylalanine residue of PCP abolishes its interaction with the eIF2AK4. Further, a genetically engineered HEV-expressing F53A mutant PCP shows poor replication efficiency. Collectively, these data identify an additional property of the g1-HEV PCP protein, through which it helps the virus in antagonizing eIF2AK4-mediated phosphorylation of the eIF2α, thus contributing to uninterrupted synthesis of viral proteins in the infected cells. IMPORTANCE Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in humans. It causes chronic infection in organ transplant patients. Although the disease is self-limiting in normal individuals, it is associated with high mortality (~30%) in pregnant women. In an earlier study, we identified the interaction between the genotype 1 HEV protease (PCP) and cellular eukaryotic initiation factor 2 alpha kinase 4 (eIF2AK4). Since eIF2AK4 is a sensor of the cellular integrated stress response machinery, we evaluated the significance of the interaction between PCP and eIF2AK4. Here, we show that PCP competitively associates with and interferes with self-association of the eIF2AK4, thereby inhibiting its kinase activity. Lack of eIF2AK4 activity prevents phosphorylation-mediated inactivation of the cellular eIF2α, which is essential for initiation of cap-dependent translation. Thus, PCP behaves as a proviral factor, promoting uninterrupted synthesis of viral proteins in infected cells, which is crucial for survival and proliferation of the virus." @default.
• W4377011867 created "2023-05-19" @default.
• W4377011867 creator A5005681022 @default.
• W4377011867 creator A5010206031 @default.
• W4377011867 creator A5022170940 @default.
• W4377011867 creator A5041083662 @default.
• W4377011867 creator A5041439693 @default.
• W4377011867 date "2023-06-29" @default.
• W4377011867 modified "2023-09-30" @default.
• W4377011867 title "Hepatitis E Virus Protease Inhibits the Activity of Eukaryotic Initiation Factor 2-Alpha Kinase 4 and Promotes Virus Survival" @default.
• W4377011867 cites W1595419937 @default.
• W4377011867 cites W1963538134 @default.
• W4377011867 cites W1976299502 @default.
• W4377011867 cites W1977655940 @default.
• W4377011867 cites W1980086230 @default.
• W4377011867 cites W1987962702 @default.
• W4377011867 cites W2032897963 @default.
• W4377011867 cites W2047910097 @default.
• W4377011867 cites W2049636398 @default.
• W4377011867 cites W2050473881 @default.
• W4377011867 cites W2056036930 @default.
• W4377011867 cites W2059916510 @default.
• W4377011867 cites W2072593285 @default.
• W4377011867 cites W2078851915 @default.
• W4377011867 cites W2084208175 @default.
• W4377011867 cites W2092238438 @default.
• W4377011867 cites W2094756522 @default.
• W4377011867 cites W2096470485 @default.
• W4377011867 cites W2098587625 @default.
• W4377011867 cites W2111627216 @default.
• W4377011867 cites W2119003997 @default.
• W4377011867 cites W2121313939 @default.
• W4377011867 cites W2122994445 @default.
• W4377011867 cites W2124045778 @default.
• W4377011867 cites W2136377881 @default.
• W4377011867 cites W2139079446 @default.
• W4377011867 cites W2142853998 @default.
• W4377011867 cites W2144447024 @default.
• W4377011867 cites W2145283241 @default.
• W4377011867 cites W2147891253 @default.
• W4377011867 cites W2151778974 @default.
• W4377011867 cites W2156146714 @default.
• W4377011867 cites W2158290219 @default.
• W4377011867 cites W2252392666 @default.
• W4377011867 cites W2314404470 @default.
• W4377011867 cites W2343472774 @default.
• W4377011867 cites W2411907574 @default.
• W4377011867 cites W2503176400 @default.
• W4377011867 cites W2515537728 @default.
• W4377011867 cites W2567987309 @default.
• W4377011867 cites W2573091838 @default.
• W4377011867 cites W2578489854 @default.
• W4377011867 cites W2735586161 @default.
• W4377011867 cites W2749841407 @default.
• W4377011867 cites W2770186875 @default.
• W4377011867 cites W2782867278 @default.
• W4377011867 cites W2784929572 @default.
• W4377011867 cites W2962634872 @default.
• W4377011867 cites W3004744912 @default.
• W4377011867 cites W3016644404 @default.
• W4377011867 cites W3019679086 @default.
• W4377011867 cites W3209011291 @default.
• W4377011867 cites W4213445308 @default.
• W4377011867 cites W4311055502 @default.
• W4377011867 doi "https://doi.org/10.1128/jvi.00347-23" @default.
• W4377011867 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37199644" @default.
• W4377011867 hasPublicationYear "2023" @default.
• W4377011867 type Work @default.
• W4377011867 citedByCount "0" @default.
• W4377011867 crossrefType "journal-article" @default.
• W4377011867 hasAuthorship W4377011867A5005681022 @default.
• W4377011867 hasAuthorship W4377011867A5010206031 @default.
• W4377011867 hasAuthorship W4377011867A5022170940 @default.
• W4377011867 hasAuthorship W4377011867A5041083662 @default.
• W4377011867 hasAuthorship W4377011867A5041439693 @default.
• W4377011867 hasConcept C104317684 @default.
• W4377011867 hasConcept C105580179 @default.
• W4377011867 hasConcept C11960822 @default.
• W4377011867 hasConcept C135763542 @default.
• W4377011867 hasConcept C140704245 @default.
• W4377011867 hasConcept C149364088 @default.
• W4377011867 hasConcept C159047783 @default.
• W4377011867 hasConcept C161238802 @default.
• W4377011867 hasConcept C184235292 @default.
• W4377011867 hasConcept C2522874641 @default.
• W4377011867 hasConcept C2777479484 @default.
• W4377011867 hasConcept C2777666129 @default.
• W4377011867 hasConcept C2780593183 @default.
• W4377011867 hasConcept C2780617729 @default.
• W4377011867 hasConcept C2780777367 @default.
• W4377011867 hasConcept C54355233 @default.
• W4377011867 hasConcept C82495950 @default.
• W4377011867 hasConcept C86803240 @default.
• W4377011867 hasConcept C90934575 @default.
• W4377011867 hasConcept C93734116 @default.
• W4377011867 hasConcept C95444343 @default.
• W4377011867 hasConcept C97029542 @default.
• W4377011867 hasConcept C97154109 @default.
• W4377011867 hasConceptScore W4377011867C104317684 @default.
• W4377011867 hasConceptScore W4377011867C105580179 @default.

• next