Retinoids inhibit measles virus through a type I IFN-dependent bystander effect

FASEB J. 2009 Sep;23(9):3203-12. doi: 10.1096/fj.09-129288. Epub 2009 May 15.


Measles-associated mortality can be decreased in response to treatment with vitamin A. Our goal was to understand the mechanism by which vitamin A and other retinoids reduce measles virus (MeV) replication in vitro. MeV is known to inhibit type I interferon (IFN) signaling, and retinoids are increasingly implicated in modulating innate immunity. Type I IFN blocking antibodies abrogated the inhibitory effects of all-trans retinoic acid (ATRA) on MeV replication (EC(50) of ATRA: 3.17 x 10(-8) M). IFN-stimulated genes (ISGs) are up-regulated by ATRA in MeV-infected U937 cell cultures starting at 12 h and reaching a plateau at 24 h postinfection when compared to either treatment or infection alone. We found that this increased gene expression occurs in uninfected cells by using a transwell system where the uninfected cells were separated from infected cells by a membrane with 0.02-muM pores. Uninfected bystander cells from the ATRA-treated transwells did not support substantial viral replication when subsequently infected with MeV. In the absence of ATRA, the cells from the uninfected chamber did not up-regulate ISG expression and were not protected from subsequent challenge with virus. These results demonstrate that retinoids inhibit MeV replication by up-regulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection during subsequent rounds of viral replication.

MeSH terms

  • Bystander Effect / drug effects*
  • Cell Line
  • Humans
  • Immunity, Innate
  • Interferon Type I / immunology*
  • Measles / diet therapy
  • Measles / prevention & control
  • Measles virus / drug effects*
  • Retinoids / pharmacology*
  • Signal Transduction / immunology
  • Tretinoin / pharmacology
  • Virus Replication / drug effects
  • Vitamin A / pharmacology


  • Interferon Type I
  • Retinoids
  • Vitamin A
  • Tretinoin