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

• Published in: PLoS pathogens Vol. 13; no. 3; p. e1006253
• Main Authors: Zhang, Xiao-Feng, Sun, Rong, Guo, Qin, Zhang, Shaoyan, Meulia, Tea, Halfmann, Randal, Li, Dawei, Qu, Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.03.2017; Public Library of Science (PLoS)
• Subjects: Agricultural management; Agricultural research; Agriculture; Agronomy; Antiviral agents; Assaying; Biology and Life Sciences; Biotechnology; Blocking; Capsid protein; Capsids; Carmovirus - physiology; Cell proliferation; Clusters; Coalescence; Coalescing; Coat protein; Complementation; Data acquisition; Data collection; Data processing; Defensive behavior; Deoxyribonucleic acid; DNA; DNA viruses; Epitopes; Flowers & plants; Food; Genetic aspects; Genetic crosses; Genetic diversity; Genetic isolation; Genomes; Hepatitis; HIV; Homology; Host plants; Human immunodeficiency virus; Immunoblotting; In vivo methods and tests; Infections; Invasions; Laboratories; Leaves; Localization; Markers; Mathematical models; Medical research; Medicine and health sciences; Microscopy, Confocal; Multiplication; Mutants; Nicotiana - virology; Offspring; Pathology; Plant diseases; Plant Diseases - virology; Plant pathology; Plant protection; Plants; Population; Population genetics; Population growth; Population structure; Position (location); Probability theory; Proteins; R&D; Replication; Research & development; Ribonucleic acid; RNA; RNA viruses; Studies; Sun; Superinfection; Superinfection - microbiology; Suppressors; Sympatric populations; Tea; Tobacco; Transgenic plants; Virology; Virus replication; Virus Replication - physiology; Viruses; West Nile virus; Wheat; Beijing China; Ohio; United States > US; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006253

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.