Researchers at Institut Pasteur of Shanghai reveal a novel function of HCoV-OC43 ns12.9 protein serves as a viroporin in morphogenesis and pathogenesis during human coronavirus infection
On September 2, Journal of Virology published a research work online entitled“The ns12.9 accessory protein of human coronavirus OC43 is a viroporin involved in virion morphogenesis and pathogenesis”from a team of researchers led by Bing Sun, Institut Pasteur of Shanghai, Chinese Academy of Sciences.
Dr. Sun Previously has demonstrated that 3a protein from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus production （PNAS，2006）. There is a similar gene which is located in human coronavirus OC43 (HCoV-OC43) encodes the ns12.9 accessory protein. However, its function during viral infection remains unknown.
Researchers engineered a recombinant mutant virus lacking the ns12.9 protein (HCoV-OC43-Δns12.9) to characterize the contributions of ns12.9 in HCoV-OC43 replication. The ns12.9 accessory protein is a transmembrane protein and forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization, suggesting that ns12.9 is a newly recognized viroporin. HCoV-OC43-Δns12.9 presented at least 10-fold reduction of viral titer in vitro and in vivo. Intriguingly, exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate the production of HCoV-OC43-Δns12.9, indicating that the ion channel activity of ns12.9 plays a significant role in the production of virus. Systematic dissection of single-cycle replication revealed that ns12.9 protein had no measurable effect on virus entry, subgenomic messenger RNA (sgmRNA) synthesis and protein expression. Further characterization revealed that HCoV-OC43-Δns12.9 was less efficient in virion morphogenesis than recombinant wild-type virus (HCoV-OC43-WT), suggesting that the ns12.9 accessory protein functions as a viroporin and which is involved in virion morphogenesis and the pathogenesis of HCoV-OC43 infection.
This study contributes to a deeper understanding of the HCoV-OC43 life cycle. In addition, the identification of ns12.9 as a viroporin may provide a good target for developing novel drugs against coronaviruses. Due to the significance of this study, the manuscript has been selected as Spotlight Feature article in Journal of virology.
The project is conducted and directed by both Prof. Bing Sun from Institute Pasteur of Shanghia, CAS and Prof. Sidong Xiong from Soochow University.
The HCoV-OC43 ns12.9 protein is a viroporin involved in virion morphogenesis. (A) The I/V curve of voltage dependencies of steady-state currents in control oocytes (filled squares) and ns12.9-expressing oocytes (filled circles). (B) Transmission electron micrographs of virions in the infected RD cells. (C) The weight variations and survival curves after wild type and mutant virus infection.