A self-perpetuating repressive state of a viral replication protein blocks superinfection by the same virus

PLoS Pathogens

Shaoyan Zhang¹  Qin Guo¹  Randal Halfmann¹  Xiao-Feng Zhang¹  Tea Meulia¹  Dawei Li²  Rong Sun³  Feng Qu⁴ 

[1] Department of Plant Pathology, The Ohio State University, Wooster, Ohio, United States of America;Molecular and Cellular Imaging Center, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio, United States of America;State Key Laboratory of Agro-Biotechnology, College of Biological Sciences, China Agricultural University, Beijing, China;Stowers Institute for Medical Research, Kansas City, Missouri, United States of America

关键词: Viral replication;    Viral genomics;    RNA viruses;    West Nile virus;    Cytoplasmic inclusions;    Hepatitis C virus;    Vesicular stomatitis virus;    Genome complexity;   

DOI  :  10.1371/journal.ppat.1006253

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Diverse animal and plant viruses block the re-infection of host cells by the same or highly similar viruses through superinfection exclusion (SIE), a widely observed, yet poorly understood phenomenon. Here we demonstrate that SIE of turnip crinkle virus (TCV) is exclusively determined by p28, one of the two replication proteins encoded by this virus. p28 expressed from a TCV replicon exerts strong SIE to a different TCV replicon. Transiently expressed p28, delivered simultaneously with, or ahead of, a TCV replicon, largely recapitulates this repressive activity. Interestingly, p28-mediated SIE is dramatically enhanced by C-terminally fused epitope tags or fluorescent proteins, but weakened by N-terminal modifications, and it inversely correlates with the ability of p28 to complement the replication of a p28-defective TCV replicon. Strikingly, p28 in SIE-positive cells forms large, mobile punctate inclusions that trans-aggregate a non-coalescing, SIE-defective, yet replication-competent p28 mutant. These results support a model postulating that TCV SIE is caused by the formation of multimeric p28 complexes capable of intercepting fresh p28 monomers translated from superinfector genomes, thereby abolishing superinfector replication. This model could prove to be applicable to other RNA viruses, and offer novel targets for antiviral therapy.

【 授权许可】

CC BY