1.A.89 The Human Coronavirus 229E Viroporin (229E Viroporin) Family 

A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Zhang et al. 2013 demonstrated that ORF4a of the human coroavirus 229E is similar to a viroporin, ORF3a, from the severe acute respiratory syndrome coronavirus (SARS-CoV). ORF4a forms ion channels and regulates virus release. When ORF4a proteins were expressed in infected cells, they localized to the endoplasmic reticulum/Golgi intermediate compartment (ERGIC) and formed homo-oligomers through disulfide bridges that possessed ion channel activity in both Xenopus oocytes and yeast. Based on the measurement of conductance to different monovalent cations, ORF4a appeared to form a non-selective channel for monovalent cations. Viral production decreased when ORF4a protein expression was suppressed by siRNA in infected cells. Thus, the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV ORF3a protein which also acts as a viroporin to regulates virus production.