tailieunhanh - Báo cáo y học: "Amino acid substitutions in the E2 glycoprotein of Sindbis-like virus XJ-160 confer the ability to undergo heparan sulfate-dependent infection of mouse embryonic fibroblasts"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Amino acid substitutions in the E2 glycoprotein of Sindbis-like virus XJ-160 confer the ability to undergo heparan sulfate-dependent infection of mouse embryonic fibroblasts | Zhu et al. Virology Journal 2010 7 225 http content 7 1 225 VIROLOGY JOURNAL SHORT REPORT Open Access Amino acid substitutions in the E2 glycoprotein of Sindbis-like virus XJ-160 confer the ability to undergo heparan sulfate-dependent infection of mouse embryonic fibroblasts Wuyang Zhu 1 Shihong Fu1 Ying He1 Jinping Li2 Guodong Liang1 Abstract We have recently demonstrated an essential role of the domain of 145-150 amino acid in the E2 glycoprotein of Sindbis virus in the interaction with cellular heparan sulfate HS and in the infection of mouse embryonic fibroblasts MEF cells. In this study we constructed and characterized the mutants of Sindbis-like virus XJ-160 in which Tyr-146 and or Asn-149 in the E2 glycoprotein had been substituted with His and Arg respectively. Unlike parental virus XJ-160 mutants with either or both substitutions were able to infect wild-type mouse embryonic fibroblasts MEF-wt or MEF-EpA cells which produce mutant HS. Significantly more infectious particles were released from MEF-wt than from MEF-EpA cells. The mutant virus with both substitutions release was inhibited by pre-incubation of virus with heparin or pre-treatment of BHK-21 cells with HS-degrading enzyme. Both XJ-160 and the mutant viruses retained substantial neurovirulence in suckling mice. Our findings provide further support to the importance of positively charged residues in the HS-binding site of E2 in mediating Sindbis virus infection of MEF cells. Findings Sindbis virus SINV is considered the prototype of Alphavirus genus Togaviridae family 1 2 . Nearly 30 members of the genus are widely distributed in all continents except in the Antarctic. Sindbis virus is an enveloped virus with an kb genome of single stranded RNA. The viral genome with a 5 terminal methylguanylate cap and a 3 terminal polyadenylate tail encodes four nonstructural proteins nsP1-4 and three mature structural proteins capsid E2 and E1 . Based on the divergence of nucleotide .