Severe Acute Respiratory Syndrome-associated Coronavirus 3a Protein Forms an Ion Channel and Modulates Virus Release

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Aug 9

PMID 16894145

Citations 170

Authors

Wei Lu

Bo-Jian Zheng

Ke Xu

Wolfgang Schwarz

Lanying Du

Charlotte K L Wong

Jiadong Chen

Shuming Duan

Vincent Deubel

Bing Sun

Affiliations

Soon will be listed here.

Abstract

Fourteen ORFs have been identified in the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) genome. ORF 3a of SARS-CoV codes for a recently identified transmembrane protein, but its function remains unknown. In this study we confirmed the 3a protein expression and investigated its localization at the surface of SARS-CoV-infected or 3a-cDNA-transfected cells. Our experiments showed that recombinant 3a protein can form a homotetramer complex through interprotein disulfide bridges in 3a-cDNA-transfected cells, providing a clue to ion channel function. The putative ion channel activity of this protein was assessed in 3a-complement RNA-injected Xenopus oocytes by two-electrode voltage clamp. The results suggest that 3a protein forms a potassium sensitive channel, which can be efficiently inhibited by barium. After FRhK-4 cells were transfected with an siRNA, which is known to suppress 3a expression, followed by infection with SARS-CoV, the released virus was significantly decreased, whereas the replication of the virus in the infected cells was not changed. Our observation suggests that SARS-CoV ORF 3a functions as an ion channel that may promote virus release. This finding will help to explain the highly pathogenic nature of SARS-CoV and to develop new strategies for treatment of SARS infection.

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