Alphavirus Receptor Breakthrough: Novel VLDLR Recognition Mechanism

A Holocene survey has detect a novel receptor recognition mechanism of VLDLR and the alphavirus EEEV . The EEEV virus , which is an alphavirus , can cause central nervous system infection lead to severe encephalitis with a mortality rate of over 30 % . scientist from the Institute of Biophysics ( IBP ) of the Chinese Academy of Sciences and Tsinghua University jointly complete the research . The survey analyze multiple high - resolution complex structure of the EEEV virion - like atom and the LDLR class angstrom repeat ( LAs ) in the extracellular region of the homo very low - density lipoprotein receptor ( VLDLR).

research_worker found three distinct receptor binding site on the surface of the alphavirus EEEV , all locate on bulge of the E1 / E2 glycoprotein trimer . The survey identify two main receptor consecutive binding manner , LA1 - 2 and LA3 - 5 , which intercede the binding between the virus and cell surface receptor as well as subsequent virus internalization . The research uncover that the introduction of the dysfunctional LA3 in VLDLR significantly enhance the attachment of EEEV to the cell.

Interestingly , the key amino acid residue K206 at site degree_centigrade is not conserve in the EEEV virus , elevation concern about the vaccine strain EEEV - PE6 which still incorporate K206 at site C. This propose a potential hazard of exploitation EEEV PE6 strain as a vaccine strain . Additionally , a mutant of the key binding site ( W50A ) in LA1 significantly reduce the virus 's ability to adsorb on the cell surface , while a mutant of the key binding site ( W132A ) in LA3 enhance the virus 's adsorption on the cell surface.

structural and functional analysis uncover that LA3 and LA1 may competitively bind at site A. The W132A mutant drive the switch from the LA3 - 5 predominate binding manner to the LA1 - 2 predominate binding manner . person with the VLDLR - W132 G mutant in their genome may be more susceptible to infection by the EEEV alphavirus . This survey supply a comprehensive_examination understanding of the complex and change receptor binding manner of the novel receptor VLDLR on the surface of the alphavirus EEEV , lend to our cognition of alphavirus ' transmission mechanisms.

In decision , the discovery of the novel receptor recognition mechanism shed light on the interaction between alphavirus and receptor . The survey 's findings rich_person significant deduction for understanding the transmission mechanism of alphavirus and could lead to potential promotion in battle alphavirus infections.