Identification and characterization of key residues in Zika virus envelope protein for virus assembly and entry

Emerging Microbes and Infections

Zhenghong Yuan¹  Zhigang Yi¹  Xiao Ma¹ 

[1] Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, and Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China;

关键词: Zika virus (ZIKV);    flavivirus;    envelope protein;    glycoprotein;    viral egress;    viral entry;   

DOI  :  10.1080/22221751.2022.2082888

来源: DOAJ

【 摘 要 】

Zika virus (ZIKV), a family member in the Flavivirus genus, has re-emerged as a global public health concern. The envelope (E) proteins of flaviviruses play a dual role in viral assembly and entry. To identify the key residues of E in virus entry, we generated a ZIKV trans-complemented particle (ZIKVTCP) system, in which a subgenomic reporter replicon was packaged by trans-complementation with expression of CprME. We performed mutagenesis studies of the loop regions that protrude from the surface of the virion in the E ectodomains (DI, DII, DIII). Most mutated ZIKVTCPs exhibited deficient egress. Mutations in DII and in the hinge region of DI and DIII affected prM expression. With a bioorthogonal system, photocrosslinking experiments identified crosslinked intracellular E trimers and demonstrated that egress-deficient mutants in DIII impaired E trimerization. Of these mutants, an E-trimerization-dead mutation D389A that nears the E-E interface between two neighbouring spikes in the immature virion completely abolished viral egress. Several mutations abolished ZIKVTCPs’ entry, without severely affecting viral egress. Further virus binding experiments demonstrated a deficiency of the mutated ZIKVTCPs in virus attachment. Strikingly, synthesized peptide containing residues of two mutants (268-273aa in DII) could bind to host cells and significantly compete for viral attachment and interfere with viral infection, suggesting an important role of these resides in virus entry. Our findings uncovered the requirement for DIII mediated-E trimerization in viral egress, and discovered a key residue group in DII that participates in virus entry.

【 授权许可】

Unknown