tetano
Editor, Senior Moderator
Transbound Emerg Dis
. 2022 Jul 20.
doi: 10.1111/tbed.14665. Online ahead of print.
PA-X Protein Assists H9N2 Subtype Avian Influenza Virus in Escaping Immune Response of Mucosal Dendritic Cells
Tao Qin[SUP] 1 2 3 4 [/SUP], Yulian Chen[SUP] 1 [/SUP], Dandan Huangfu[SUP] 1 [/SUP], Yinyan Yin[SUP] 5 [/SUP], Xinyu Miao[SUP] 1 [/SUP], Yuncong Yin[SUP] 1 2 3 4 [/SUP], Sujuan Chen[SUP] 1 2 3 4 [/SUP], Daxin Peng[SUP] 1 2 3 4 [/SUP], Xiufan Liu[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
H9N2 subtype low pathogenicity avian influenza virus (AIV) poses a potential zoonotic risk. PA-X, a novel protein generated by PA gene ribosomal frameshift, is considered to be the virulence factor of H9N2 subtype AIVs. Our study found that rTX possessing PA-X protein enhanced the mammalian pathogenicity of H9N2 subtype AIVs compared with PA-X-deficient virus (rTX-FS). Furthermore, PA-X protein inhibited H9N2 subtype AIVs to infect dendritic cells (DCs), but not nonimmune cells (MDCK cells). Meanwhile, PA-X protein suppressed the phenotypic expression (CD80, CD86, CD40, and MHCII), early activation markers (CD69), and pro-inflammatory cytokines (IL-6 and TNF-α), whereas increased anti-inflammatory cytokine (IL-10) in DCs. After intranasally viral infection in mice, we found that PA-X protein of H9N2 subtype AIVs reduced CD11b[SUP]+[/SUP] and CD103[SUP]+[/SUP] subtype mucosal DCs recruitment to the nasal submucosa by inhibiting CCL20 expression. Moreover, PA-X protein abolished the migratory ability of CD11b[SUP]+[/SUP] and CD103[SUP]+[/SUP] DCs into draining cervical lymph nodes (CLNs) by downregulating CCR7 expression. The rTX-infected DCs significantly impaired the allogeneic CD4[SUP]+[/SUP] T cell proliferation, suggesting PA-X protein suppressed the immune functions of DCs for hindering the downstream immune activation. These findings indicated that PA-X protein assisted H9N2 subtype AIVs in escaping immune response of mucosal DCs for enhancing the pathogenicity. This article is protected by copyright. All rights reserved.
Keywords: Avian influenza virus; Dendritic cells; H9N2; Innate immunity; PA-X protein; Pathogenicity.
. 2022 Jul 20.
doi: 10.1111/tbed.14665. Online ahead of print.
PA-X Protein Assists H9N2 Subtype Avian Influenza Virus in Escaping Immune Response of Mucosal Dendritic Cells
Tao Qin[SUP] 1 2 3 4 [/SUP], Yulian Chen[SUP] 1 [/SUP], Dandan Huangfu[SUP] 1 [/SUP], Yinyan Yin[SUP] 5 [/SUP], Xinyu Miao[SUP] 1 [/SUP], Yuncong Yin[SUP] 1 2 3 4 [/SUP], Sujuan Chen[SUP] 1 2 3 4 [/SUP], Daxin Peng[SUP] 1 2 3 4 [/SUP], Xiufan Liu[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 35855630
- DOI: 10.1111/tbed.14665
Abstract
H9N2 subtype low pathogenicity avian influenza virus (AIV) poses a potential zoonotic risk. PA-X, a novel protein generated by PA gene ribosomal frameshift, is considered to be the virulence factor of H9N2 subtype AIVs. Our study found that rTX possessing PA-X protein enhanced the mammalian pathogenicity of H9N2 subtype AIVs compared with PA-X-deficient virus (rTX-FS). Furthermore, PA-X protein inhibited H9N2 subtype AIVs to infect dendritic cells (DCs), but not nonimmune cells (MDCK cells). Meanwhile, PA-X protein suppressed the phenotypic expression (CD80, CD86, CD40, and MHCII), early activation markers (CD69), and pro-inflammatory cytokines (IL-6 and TNF-α), whereas increased anti-inflammatory cytokine (IL-10) in DCs. After intranasally viral infection in mice, we found that PA-X protein of H9N2 subtype AIVs reduced CD11b[SUP]+[/SUP] and CD103[SUP]+[/SUP] subtype mucosal DCs recruitment to the nasal submucosa by inhibiting CCL20 expression. Moreover, PA-X protein abolished the migratory ability of CD11b[SUP]+[/SUP] and CD103[SUP]+[/SUP] DCs into draining cervical lymph nodes (CLNs) by downregulating CCR7 expression. The rTX-infected DCs significantly impaired the allogeneic CD4[SUP]+[/SUP] T cell proliferation, suggesting PA-X protein suppressed the immune functions of DCs for hindering the downstream immune activation. These findings indicated that PA-X protein assisted H9N2 subtype AIVs in escaping immune response of mucosal DCs for enhancing the pathogenicity. This article is protected by copyright. All rights reserved.
Keywords: Avian influenza virus; Dendritic cells; H9N2; Innate immunity; PA-X protein; Pathogenicity.