@article{9986b44a508b46168a1259dab73b95ad,
title = "Effects of an in-frame deletion of the 6k gene locus from the genome of Ross River virus",
abstract = "The alphaviral 6k gene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the 6k proteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel 6k in-frame deletion mutant. Comprehensive microscopic analysis revealed that the 6k proteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the 6k proteins 6K and TF [RRV-(¿6K)] were more vulnerable to changes in pH, and the corresponding virus had increased sensitivity to a higher temperature. While the 6k deletion did not reduce RRV particle production in BHK-21 cells, it affected virion release from the host cell. Subsequent in vivo studies demonstrated that RRV-(¿6K) caused a milder disease than wild-type virus, with viral titers being reduced in infected mice. Immunization of mice with RRV-(¿6K) resulted in a reduced viral load and accelerated viral elimination upon secondary infection with wild-type RRV or another alphavirus, chikungunya virus (CHIKV). Our results show that the 6k proteins may contribute to alphaviral disease manifestations and suggest that manipulation of the 6k gene may be a potential strategy to facilitate viral vaccine development.",
author = "Adam Taylor and Julian Melton and Lara Herrero and Bastian Thaa and Liis Karo-Astover and Peter Gage and Michelle Nelson and Kuo-Ching Sheng and Brett Lidbury and Gary Ewart and Gerald McInerney and Andres Merits and Suresh MAHALINGAM",
note = "Funding Information: We thank Pontus Aspenstr{\"o}m, Karin Lor{\'e}, and Lisa Westerberg (Karolinska Institutet, Stockholm, Sweden) for the generous provision of reagents. Part of this work was supported by a National Health and Medical Research Council grant to S.M. (grant 399700) and a Swedish Research Council grant (621-2014-4718) to G.M.M. A.T. is the recipient of a National Health and Medical Research Council early career research fellowship (1073108). L.J.H. is the recipient of an Australian Research Council Discovery early career researcher award (140101493). S.M. is the recipient of a National Health and Medical Research Council senior research fellowship (1059167). Department of Health | National Health and Medical Research Council (NHMRC) provided funding to Suresh Mahalingam under grant numbers 399700, 1047252, and 1059167. Svenska Forskningsr{\aa}det Formas (Swedish Research Council Formas) provided funding to GeraldMichael McInerney under grant number 621-2014-4718. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} 2016, American Society for Microbiology.",
year = "2016",
doi = "10.1128/JVI.03192-15",
language = "English",
volume = "90",
pages = "4150--4159",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",
}