Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 8296-8306 |
| Number of pages | 11 |
| Journal | Journal of virology |
| Volume | 82 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Sep 1 2008 |
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All Science Journal Classification (ASJC) codes
- Microbiology
- Immunology
- Insect Science
- Virology
Cite this
Measles virus circumvents the host interferon response by different actions of the C and V proteins. / Nakatsu, Yuichiro; Takeda, Makoto; Ohno, Shinji; Shirogane, Yuta; Iwasaki, Masaharu; Yanagi, Yusuke.
In: Journal of virology, Vol. 82, No. 17, 01.09.2008, p. 8296-8306.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Measles virus circumvents the host interferon response by different actions of the C and V proteins
AU - Nakatsu, Yuichiro
AU - Takeda, Makoto
AU - Ohno, Shinji
AU - Shirogane, Yuta
AU - Iwasaki, Masaharu
AU - Yanagi, Yusuke
PY - 2008/9/1
Y1 - 2008/9/1
N2 - 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.
AB - 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.
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U2 - 10.1128/JVI.00108-08
DO - 10.1128/JVI.00108-08
M3 - Article
VL - 82
SP - 8296
EP - 8306
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 17
ER -