siRNA silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in Vero E6 cells.
The outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 has had a significant impact worldwide. No effective prophylaxis or treatment for SARS is available up to now. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-associated coronavirus (SARS-CoV). By expressing a U6 promoter-driven small interfering RNA containing sequences homologous to part of ACE2 mRNA, we successfully silenced ACE2 expression in Vero E6 cells. By detecting negative strand SARS-CoV RNA and measuring RNA copy numbers of SARS-CoV by real-time reverse transcription polymerase chain reaction (RT-PCR), we demonstrated that SARS-CoV infection was reduced in the ACE2-silenced cell lines. These findings support the involvement of ACE2 in SARS-CoV infections and provide a basis for further studies on potential use of siRNA targeting ACE2 as a preventive or therapeutic strategy for SARS.
Lu
C-Y
CY
Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan. cylu@ntuh.gov.tw
Huang
H-Y
HY
Yang
T-H
TH
Chang
L-Y
LY
Lee
C-Y
CY
Huang
L-M
LM
D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002415:Cats; D002460:Cell Line; D002522:Chlorocebus aethiops; D020868:Gene Silencing / Q000187:drug effects*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D034741:RNA, Small Interfering; D007703:Peptidyl-Dipeptidase A; D000085962:Angiotensin-Converting Enzyme 2