CD151, A Novel Host Factor of Nuclear Export Signaling in Influenza Virus Infection

Publication date: Available online 21 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Yongkang Qiao, Yan Yan, Kai Sen Tan, Sheryl SL. Tan, Ju Ee Seet, Thiruma Valavan Arumugam, Vincent TK. Chow, De Yun Wang, Thai Tran
BackgroundDespite 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.ObjectivesTo 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.MethodsWe 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.ResultsAs compared with wild-type infected mice, CD151-null infected mice exhibited significant reduction in virus titer and improvement in survival that is associated with pronounced host anti-viral 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.ConclusionsOur 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 utilizes 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.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CSqIlX