tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2018 Jan 16. pii: 201706928. doi: 10.1073/pnas.1706928115. [Epub ahead of print]
[h=1]MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape.[/h] Menachery VD[SUP]1,[/SUP][SUP]2[/SUP], Sch?fer A[SUP]2[/SUP], Burnum-Johnson KE[SUP]3[/SUP], Mitchell HD[SUP]3[/SUP], Eisfeld AJ[SUP]4[/SUP], Walters KB[SUP]4[/SUP], Nicora CD[SUP]3[/SUP], Purvine SO[SUP]3[/SUP], Casey CP[SUP]3[/SUP], Monroe ME[SUP]3[/SUP], Weitz KK[SUP]3[/SUP], Stratton KG[SUP]3[/SUP], Webb-Robertson BM[SUP]3[/SUP], Gralinski LE[SUP]2[/SUP], Metz TO[SUP]3[/SUP], Smith RD[SUP]3[/SUP], Waters KM[SUP]3[/SUP], Sims AC[SUP]2[/SUP], Kawaoka Y[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Baric RS[SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ-dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV-mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.
[h=4]KEYWORDS:[/h] DNA methylation; antigen presentation; coronavirus; epigenetics; influenza
PMID: 29339515 DOI: 10.1073/pnas.1706928115
Free full text
[h=1]MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape.[/h] Menachery VD[SUP]1,[/SUP][SUP]2[/SUP], Sch?fer A[SUP]2[/SUP], Burnum-Johnson KE[SUP]3[/SUP], Mitchell HD[SUP]3[/SUP], Eisfeld AJ[SUP]4[/SUP], Walters KB[SUP]4[/SUP], Nicora CD[SUP]3[/SUP], Purvine SO[SUP]3[/SUP], Casey CP[SUP]3[/SUP], Monroe ME[SUP]3[/SUP], Weitz KK[SUP]3[/SUP], Stratton KG[SUP]3[/SUP], Webb-Robertson BM[SUP]3[/SUP], Gralinski LE[SUP]2[/SUP], Metz TO[SUP]3[/SUP], Smith RD[SUP]3[/SUP], Waters KM[SUP]3[/SUP], Sims AC[SUP]2[/SUP], Kawaoka Y[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Baric RS[SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ-dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV-mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.
[h=4]KEYWORDS:[/h] DNA methylation; antigen presentation; coronavirus; epigenetics; influenza
PMID: 29339515 DOI: 10.1073/pnas.1706928115
Free full text