CD151, a novel host factor of nuclear export signaling in influenza virus infection - 04/05/18
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Abstract |
Background |
Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown.
Objectives |
We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains.
Methods |
We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro–differentiated human nasal epithelial cells cultured at air-liquid interface.
Results |
As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly.
Conclusions |
Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Influenza A virus (IAV), CD151, nuclear export, host innate immunity, inflammasome, IAV severity
Abbreviations used : ALI, ATCC, dpi, hNECs, IAV, M1, NEP, NP, NS1, PFU, Poly (I:C), qPCR, siRNA, vRNP, WT
Plan
Part of this work was presented at the Nature Conference on Viral Infection and Immune Response, Wuhan, 21-24 October 2016, and the European Academy of Allergy and Clinical Immunology Annual Congress, Helsinki, 17-21 June 2017. |
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This research is supported in part by the Singapore Ministry of Health's National Medical Research Council (NMRC) under its Individual Research Grant (IRG) scheme (grant no. NMRC/1215/2009 to T.T.), the Academic Research Fund Tier 2 grant (grant no. MOE2015-T2-2 to T.T.), and the NMRC (grant nos. NMRC/CIRG/1362/2013 and NMRC/CIRG/1458/2016 to D.Y.W). |
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Disclosure of potential conflict of interest: V. T. K. Chow's institution received a grant from the Ministry of Education, Singapore. D. Y. Wang's institution received a grant from the National Medical Research Council (NMRC) of Singapore for this work and is employed by the National University of Singapore. T. Tran's institute received a grant from the NMRC of Singapore (grant no. NMRC/1215/2009) and an academic research fund (Tier 2 grant no. MOE2015-T2-2) for this work. T. Tran personally received support for travel from the same grant for this work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 5
P. 1799-1817 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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