MXD1 regulates the H9N2 and H1N1 influenza A virus-induced chemokine expression and their replications in human macrophage.

Autor: Yim HCH; Microbiome Research Centre, St George and Sutherland Clinical School, The University of New South Wales, Sydney, Australia., Leon TYY; Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Region, P.R. China., Li JCB; Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong Special Administrative Region, P.R. China.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2020 Nov; Vol. 108 (5), pp. 1631-1640. Date of Electronic Publication: 2020 Aug 13.
DOI: 10.1002/JLB.4MA0620-703RR
Abstrakt: Human infection with influenza A/Hong Kong/156/97 (H5N1) avian influenza virus is associated with a high mortality rate of 60%. This virus is originated from influenza A/Quail/Hong Kong/G1/97 (H9N2/G1) avian influenza virus. Since the 1990s, four lineages of H9N2 viruses have been circulating in poultry and cause occasional infection in humans in different countries. Due to its zoonotic and genetic reassortment potential, H9N2/G1 and H5N1 viruses are believed to be the next pandemic candidates. Previous reports, including ours, showed that the virulence of avian virus strains correlates with their ability to dysregulate cytokine expression, including TNF-α, CXCL10, and related chemokines in the virus-infected cells. However, the transcriptional factors required for this cytokine dysregulation remains undefined. In light of our previous report showing the unconventional role of MYC, an onco-transcriptional factor, for regulating the antibacterial responses, we hypothesize that the influenza virus-induced cytokine productions may be governed by MYC/MAX/MXD1 network members. Here, we demonstrated that the influenza A/Hong Kong/54/98 (H1N1)- or H9N2/G1 virus-induced CXCL10 expressions can be significantly attenuated by knocking down the MXD1 expression in primary human blood macrophages. Indeed, only the MXD1 expression was up-regulated by both H1N1 and H9N2/G1 viruses, but not other MYC/MAX/MXD1 members. The MXD1 expression and the CXCL10 hyperinduction were dependent on MEK1/2 activation. By using EMSAs, we revealed that MXD1 directly binds to the CXCL10 promoter-derived oligonucleotides upon infection of both viruses. Furthermore, silencing of MXD1 decreased the replication of H9N2 but not H1N1 viruses. Our results provide a new insight into the role of MXD1 for the pathogenicity of avian influenza viruses.
(©2020 Society for Leukocyte Biology.)
Databáze: MEDLINE
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