Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes

PLoS Pathogens

Andrew F. van den Hurk¹  Ezequiel Balmori Melian¹  Fangyao Du¹  Nick Owens¹  Stephen Rudd¹  Tomoko Nagasaki²  Roy A. Hall²  Richard A. Bowen³  Angela M. Bosco-Lauth³  Aaron C. Brault⁴  Alexander A. Khromykh⁵  Sonja Hall-Mendelin⁵ 

[1] Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, St. Lucia, Queensland, Australia;Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America;Division of Vector-Borne Diseases, Centers for Disease Prevention and Control, Fort Collins, Colorado, United States of America;Queensland Facility for Advanced Bioinformatics (QFAB), University of Queensland, Brisbane, Queensland, Australia;Virology, Public and Environmental Health, Forensic and Scientific Services, Department of Health, Queensland Government, Coopers Plains, Queensland, Australia

关键词: Mosquitoes;    Viral replication;    West Nile virus;    Structural proteins;    Gene expression;    Birds;    Viral gene expression;    Virions;   

DOI  :  10.1371/journal.ppat.1004447

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed −1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1′. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.

【 授权许可】

CC BY