Evasion of host defenses by measles virus: wild-type measles virus infection interferes with induction of Alpha/Beta interferon production.
Measles is a highly contagious disease currently responsible for over one million childhood deaths, particularly in the developing world. Since alpha/beta interferons (IFNs) are pivotal players both in nonspecific antiviral immunity and in specific cellular responses, their induction or suppression by measles virus (MV) could influence the outcome of a viral infection. In this study we compare the IFN induction and sensitivity of laboratory-passaged attenuated MV strains Edmonston and Moraten with those of recent wild-type viruses isolated and passaged solely on human peripheral blood mononuclear cells (PBMC) or on the B958 marmoset B-cell line. We report that two PBMC-grown wild-type measles isolates and two B958-grown strains of MV induce 10- to 80-fold-lower production of IFN by phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) compared to Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN-inducing MV isolates prevents Edmonston-induced but not double-stranded-RNA-induced IFN production. This suggests that the wild-type viruses can actively inhibit Edmonston-induced IFN synthesis and that this is not occurring by double-stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV to the effect of IFN. MV is thus able to suppress the synthesis of the earliest mediator of antiviral immunity, IFN-alpha/beta. This could have important implications in the virulence and spread of MV.
Naniche
D
D
Division of Virology, Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA. naniche@scripps.edu
Yeh
A
A
Eto
D
D
Manchester
M
M
Friedman
R M
RM
Oldstone
M B
MB
D000818:Animals; D002144:Callithrix; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology*; D008458:Measles Vaccine; D008459:Measles virus / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity*; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D014779:Virus Replication
D016898:Interferon-alpha; D008458:Measles Vaccine; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D016899:Interferon-beta