CD151, a novel host factor of nuclear export signaling in influenza virus infection
| Autor: | Ju Ee Seet, Yongkang Qiao, Yan Yan, De Yun Wang, Sheryl S.L. Tan, Thai Tran, Thiruma V. Arumugam, Kai Sen Tan, Vincent T. K. Chow |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Tetraspanins Immunology Tetraspanin 24 Biology Virus Replication medicine.disease_cause Virus Cell Line Mice Viral Proteins 03 medical and health sciences Influenza A Virus H1N1 Subtype 0302 clinical medicine Orthomyxoviridae Infections Tetraspanin Influenza Human Influenza A virus medicine Animals Humans Immunology and Allergy Nuclear export signal Host factor Cell Nucleus Influenza A Virus H3N2 Subtype Epithelial Cells Inflammasome Virology Immunity Innate Nucleoprotein Mice Inbred C57BL 030104 developmental biology Viral replication 030220 oncology & carcinogenesis Host-Pathogen Interactions Signal Transduction medicine.drug |
| Zdroj: | Journal of Allergy and Clinical Immunology. 141:1799-1817 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2017.11.032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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