In vitro inhibition of mumps virus by retinoids.
BACKGROUND
Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeV in vitro.


METHODS
Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot.


RESULTS
The current work demonstrates that retinoids inhibit MuV in vitro due to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours.


CONCLUSIONS
These results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection.
Kaitlin J
KJ
Soye
Claire
C
Trottier
Thomas Z
TZ
Di Lenardo
Katherine H
KH
Restori
Lee
L
Reichman
Wilson H
WH
Miller
Research Institute of the McGill University Health Center, Department of Infectious Diseases, McGill University, Montreal, Quebec, Canada. brian.ward@mcgill.ca.
Brian J
BJ
Ward
D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D008826:Microbial Sensitivity Tests; D009109:Mumps virus / Q000187:drug effects* / Q000502:physiology; D012367:RNA, Viral / Q000032:analysis; D012176:Retinoids / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral; D012176:Retinoids; D014764:Viral Proteins