Measles virus circumvents the host interferon response by different actions of the C and V proteins.
Measles is an acute febrile infectious disease with high morbidity and mortality. The genome of measles virus (MV), the causative agent, encodes two accessory products, V and C proteins, that play important roles in MV virulence. The V but not the C protein of the IC-B strain (a well-characterized virulent strain of MV) has been shown to block the Jak/Stat signaling pathway and counteract the cellular interferon (IFN) response. We have recently shown that a recombinant IC-B strain that lacks C protein expression replicates poorly in certain cell lines, and its growth defect is related to translational inhibition and strong IFN induction. Here, we show that the V protein of the MV IC-B strain also blocks the IFN induction pathway mediated by the melanoma differentiation-associated gene 5 product, thus actively interfering with the host IFN response at two different steps. On the other hand, the C protein per se possesses no activity to block the IFN induction pathway. Our data indicate that the C protein acts as a regulator of viral RNA synthesis, thereby acting indirectly to suppress IFN induction. Since recombinant MVs with C protein defective in modulating viral RNA synthesis or lacking C protein expression strongly stimulate IFN production, in spite of V protein production, both the C and V proteins must be required for MV to fully circumvent the host IFN response.
Nakatsu
Yuichiro
Y
Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Takeda
Makoto
M
Ohno
Shinji
S
Shirogane
Yuta
Y
Iwasaki
Masaharu
M
Yanagi
Yusuke
Y
D000818:Animals; D002522:Chlorocebus aethiops; D019085:Fluorescent Antibody Technique, Direct; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D007372:Interferons / Q000378:metabolism*; D049410:Luciferases, Renilla / Q000378:metabolism; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D010957:Plasmids; D014176:Protein Biosynthesis / Q000502:physiology; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
D010750:Phosphoproteins; C069181:V protein, measles virus; D014764:Viral Proteins; D007372:Interferons; D049410:Luciferases, Renilla