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.



Zhang R., Wang K., Lv W., Yu W., Xie S., Xu K., Schwarz W., Xiong S. and Sun B. (2014). The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production. Biochim Biophys Acta. 1838(4):1088-95.


TC#NameOrganismal TypeExample

ORF4a viroporin of 133 aas and 3 TMSs (Zhang et al. 2013).


ORF4a of human coronavirus 229E


Viroporin of 222 aas and 3 strongly hydrophobic TMSs in the N-terminal half of the protein followed by a region of moderate hydrophobicity in the C-terminal half.


Viroporin of human coronavirus NL63


Non structural protein 3c, a viroporin of 237 aas with 3 stronly hydrophobic TMSs in the N-terminal half of the protein and a broad region of moderate hydrophobicity in the second half.


Viroporin 3c of feline coronavirus UUF


Viroporin ORF3-1 of 205 aas and 4 or more TMSs in a 3 + 1-3 TMS arrangement.


Orf3-1 viroporin of porcine respiratory coronavirus


3a protein of 152 aas and 3 or 4 TMSs

Protein 3a of Bat coronavirus


ORF3 protein of 228 aas and 3 TMSs.

ORF3 of Chaerephon bat coronavirus/Kenya