Abstract:Heat shock proteins (HSPs) are a protein family that respond to physiological stress, such as heat, starvation, and infection. As cellular protein chaperones, they play an important role in protein folding, assembly, and degradation. Though it is well known that HSP27 is involved in a range of viral infections, its role during an encephalomyocarditis virus (EMCV) infection is not known. Here, we report that EMCV degrades HSP27 and that EMCV proteins 2Cpro and 3Apro are primarily responsible for its degradation… Show more
“…Treated or untreated cells were inoculated with the EMCV PV2 strain (0.0001 MOI) for 12 h, 24 h, and 36 h. The viral stocks and viral RNA were obtained as described previously [ 18 ]. Subsequently, the EMCV 3D gene was detected using the method of Taqman probe RT-qPCR mentioned in reference [ 15 ].…”
Section: Methodsmentioning
confidence: 99%
“…Except for these host proteins, such as Tyrosine Kinase Non-Receptor 2 (TNK2), Wiskott-Aldrich Syndrome protein Like protein (WASL), Non-Catalytic Region of Tyrosine Kinase (NCK1), the disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), and Caveolin-1, directly regulating EMCV entry [ 12 , 13 , 14 ], the heat shock protein 90β (HSP90β) [ 15 ], zinc-finger FYVE domain-containing protein (ZFYVE1) [ 16 ], and members of the tripartite motif 3 (TRIM13) [ 17 ] have also been found to indirectly facilitate viral replication by targeting the innate immune signaling pathway. In addition, host proteins heat shock protein 27 (HSP27) [ 18 ] and Members of the tripartite motif 7 (TRIM7) [ 19 ] suppress viral proliferation by positively regulating the innate immune response.…”
Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-β and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation–inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.
“…Treated or untreated cells were inoculated with the EMCV PV2 strain (0.0001 MOI) for 12 h, 24 h, and 36 h. The viral stocks and viral RNA were obtained as described previously [ 18 ]. Subsequently, the EMCV 3D gene was detected using the method of Taqman probe RT-qPCR mentioned in reference [ 15 ].…”
Section: Methodsmentioning
confidence: 99%
“…Except for these host proteins, such as Tyrosine Kinase Non-Receptor 2 (TNK2), Wiskott-Aldrich Syndrome protein Like protein (WASL), Non-Catalytic Region of Tyrosine Kinase (NCK1), the disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), and Caveolin-1, directly regulating EMCV entry [ 12 , 13 , 14 ], the heat shock protein 90β (HSP90β) [ 15 ], zinc-finger FYVE domain-containing protein (ZFYVE1) [ 16 ], and members of the tripartite motif 3 (TRIM13) [ 17 ] have also been found to indirectly facilitate viral replication by targeting the innate immune signaling pathway. In addition, host proteins heat shock protein 27 (HSP27) [ 18 ] and Members of the tripartite motif 7 (TRIM7) [ 19 ] suppress viral proliferation by positively regulating the innate immune response.…”
Histone H1.2 is a member of the linker histone family, which plays extensive and crucial roles not only in the regulation of chromatin dynamics, cell cycle, and cell apoptosis, but also in viral diseases and innate immunity response. Recently, it was discovered that H1.2 regulates interferon-β and inhibits influenza virus replication, whereas its role in other viral infections is poorly reported. Here, we first found the up-regulation of H1.2 during Encephalomyocarditis virus (EMCV) infection, implying that H1.2 was involved in EMCV infection. Overexpression of H1.2 inhibited EMCV proliferation, whereas knockdown of H1.2 showed a significant promotion of virus infection in HEK293T cells. Moreover, we demonstrated that overexpression of H1.2 remarkably enhanced the production of EMCV-induced type I interferon, which may be the crucial factor for H1.2 proliferation–inhibitory effects. We further found that H1.2 up-regulated the expression of the proteins of the MDA5 signaling pathway and interacted with MDA5 and IRF3 in EMCV infection. Further, we demonstrated that H1.2 facilitated EMCV-induced phosphorylation and nuclear translocation of IRF3. Briefly, our research uncovers the mechanism of H1.2 negatively regulating EMCV replication and provides new insight into antiviral targets for EMCV.
“…EMCV 3A also inhibited IFN signalling pathway. Interestingly, 3A does not act directly on the signalling pathway adaptor protein, but rather degrades the host chaperone protein heat shock protein 27 (HSP27), which in turn influences the stability of MDA5 for the purpose of evading the innate immune response to promote self-proliferation [ 24 ]. Figure 2.…”
“…Many viral proteins interact with HSPs. During EMCV infections, HSP27 functions as a host factor that combats EMCV infection and enhances the generation of type I IFNs triggered by EMCV [ 24 ]. Furthermore, HSP27 acts as a molecular chaperone, enhancing the EMCV-induced MDA5 signalling pathway through the stabilization of MDA5 expression.…”
Section: Host Proteins Involved In Modulating Emcv-mediated Innate Im...mentioning
A variety of animals can be infected by encephalomyocarditis virus (EMCV). EMCV is the established causative agent of myocarditis and encephalitis in some animals. EMCV causes high fatality in suckling and weaning piglets, making pigs the most susceptible domestic animal species. Importantly, EMCV has zoonotic potential to infect the human population. The ability of the pathogen to avoid and undermine the initial defence mechanism of the host contributes to its virulence and pathogenicity. A large body of literature highlights the intricate strategies employed by EMCV to escape the innate immune machinery to suit its “pathogenic needs.” Here, we also provide examples on how EMCV interacts with certain host proteins to dampen the infection process. Hence, this concise review aims to summarize these findings in a compendium of decades of research on this exciting yet underappreciated topic.
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