tetano
Editor, Senior Moderator
Front Immunol. 2019 May 29;10:1158. doi: 10.3389/fimmu.2019.01158. eCollection 2019.
[h=1]Downregulation of MHC Class I Expression by Influenza A and B Viruses.[/h] Koutsakos M[SUP]1[/SUP], McWilliam HEG[SUP]1,[/SUP][SUP]2[/SUP], Aktepe TE[SUP]1[/SUP], Fritzlar S[SUP]1[/SUP], Illing PT[SUP]3[/SUP], Mifsud NA[SUP]3[/SUP], Purcell AW[SUP]3[/SUP], Rockman S[SUP]1,[/SUP][SUP]4[/SUP], Reading PC[SUP]1,[/SUP][SUP]5[/SUP], Vivian JP[SUP]3,[/SUP][SUP]6[/SUP], Rossjohn J[SUP]3,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Brooks AG[SUP]1[/SUP], Mackenzie JM[SUP]1[/SUP], Mintern JD[SUP]2[/SUP], Villadangos JA[SUP]1,[/SUP][SUP]2[/SUP], Nguyen THO[SUP]1[/SUP], Kedzierska K[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8[SUP]+[/SUP] T cells to recognize viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8[SUP]+[/SUP] T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8[SUP]+[/SUP] T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses.
[h=4]KEYWORDS:[/h] HLA; MHC-I; T cells; influenza A virus; influenza B virus
PMID: 31191533 PMCID: PMC6548845 DOI: 10.3389/fimmu.2019.01158
[h=1]Downregulation of MHC Class I Expression by Influenza A and B Viruses.[/h] Koutsakos M[SUP]1[/SUP], McWilliam HEG[SUP]1,[/SUP][SUP]2[/SUP], Aktepe TE[SUP]1[/SUP], Fritzlar S[SUP]1[/SUP], Illing PT[SUP]3[/SUP], Mifsud NA[SUP]3[/SUP], Purcell AW[SUP]3[/SUP], Rockman S[SUP]1,[/SUP][SUP]4[/SUP], Reading PC[SUP]1,[/SUP][SUP]5[/SUP], Vivian JP[SUP]3,[/SUP][SUP]6[/SUP], Rossjohn J[SUP]3,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Brooks AG[SUP]1[/SUP], Mackenzie JM[SUP]1[/SUP], Mintern JD[SUP]2[/SUP], Villadangos JA[SUP]1,[/SUP][SUP]2[/SUP], Nguyen THO[SUP]1[/SUP], Kedzierska K[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Manipulation of the MHC-I presentation pathway, and thus limiting MHC-I cell surface expression, is used by many viruses to evade immune recognition. In particular, downregulation of MHC-I molecules at the cell surface can reduce the ability of CD8[SUP]+[/SUP] T cells to recognize viral peptides presented by MHC-I molecules and thereby delay viral clearance by CD8[SUP]+[/SUP] T cells. To date, MHC-I downregulation by influenza viruses has not been reported. Given that influenza virus infections are a global health concern and that CD8[SUP]+[/SUP] T cells play an important role in promoting influenza virus clearance and recovery from influenza disease, we investigated whether influenza A and B viruses (IAV, IBV) downregulated MHC-I as a novel mechanism to evade cellular immunity. Here, we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. This observation was consistent across a panel of class I-reduced (C1R) cell lines expressing 14 different HLA-A or -B alleles and a panel of 721.221 cell lines expressing 11 HLA-C alleles. Interestingly, IBV infection caused more pronounced reduction in surface MHC-I expression compared to IAV. Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation. Our data demonstrated that while IAV caused a global loss of MHC-I within influenza-infected cells, IBV infection resulted in the preferential loss of MHC-I molecules from the cell surface, consequent of delayed MHC-I trafficking to the cell surface, resulting from retaining MHC-I intracellularly during IBV infection. Overall, our study suggests that influenza viruses across both IAV and IBV subtypes have the potential to downregulate MHC-I surface expression levels. Our findings provide new insights into the host-pathogen interaction of influenza A and B viruses and inform the design of novel vaccine strategies against influenza viruses.
[h=4]KEYWORDS:[/h] HLA; MHC-I; T cells; influenza A virus; influenza B virus
PMID: 31191533 PMCID: PMC6548845 DOI: 10.3389/fimmu.2019.01158