EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.
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06/05/2016
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Resumo |
Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease. |
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application/pdf |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Currier , M G , Lee , S , Stobart , C C , Hotard , A L , Villenave , R , Meng , J , Pretto , C , Shields , M D , Nguyen , M T , Todd , S O , Chi , M H , Hammonds , J , Krumm , S A , Spearman , P , Plemper , R K , Sakamoto , K , Peebles , R S , Power , U F & Moore , M L 2016 , ' EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression. ' PLoS Pathogens , vol 12 , no. 5 . DOI: 10.1371/journal.ppat.1005622 |
Tipo |
article |