Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Hemoglobin subunit beta interacts with the capsid protein and antagonizes the growth of classical swine fever virus
AU - Li, Dan
AU - Dong, Hong
AU - Li, Su
AU - Munir, Muhammad
AU - Chen, Jianing
AU - Luo, Yuzi
AU - Sun, Yuan
AU - Liu, Lihong
AU - Qiu, Hua-Ji
PY - 2013/5
Y1 - 2013/5
N2 - The capsid (C) protein of the Flaviviridae family members is involved in nucleocapsid formation and virion assembly. However, the influence of C protein-interacting partners on the outcome of pestivirus infections is poorly defined. In this study, hemoglobin subunit beta (HB) was identified as a C protein-binding protein by glutathione S-transferase pulldown and subsequent mass spectrometry analysis of PK-15 cells, which are permissive cells for classical swine fever virus (CSFV). Coimmunoprecipitation and confocal microscopy confirmed that HB interacts and colocalizes with the C protein in the cytoplasm. Silencing of HB with small interfering RNAs promoted CSFV growth and replication, whereas overexpression of HB suppressed CSFV replication and growth. Interestingly, HB was found to interact with retinoic acid-inducible gene I and increase its expression, resulting in increased production of type I interferon (IFN). However, HB was unable to suppress CSFV growth when the RIG-I pathway was blocked. Overall, our results suggest that cellular HB antagonizes CSFV growth and replication by triggering IFN signaling, and might represent a novel antiviral restriction factor. This study reports for the first time the novel role of HB in innate immunity.
AB - The capsid (C) protein of the Flaviviridae family members is involved in nucleocapsid formation and virion assembly. However, the influence of C protein-interacting partners on the outcome of pestivirus infections is poorly defined. In this study, hemoglobin subunit beta (HB) was identified as a C protein-binding protein by glutathione S-transferase pulldown and subsequent mass spectrometry analysis of PK-15 cells, which are permissive cells for classical swine fever virus (CSFV). Coimmunoprecipitation and confocal microscopy confirmed that HB interacts and colocalizes with the C protein in the cytoplasm. Silencing of HB with small interfering RNAs promoted CSFV growth and replication, whereas overexpression of HB suppressed CSFV replication and growth. Interestingly, HB was found to interact with retinoic acid-inducible gene I and increase its expression, resulting in increased production of type I interferon (IFN). However, HB was unable to suppress CSFV growth when the RIG-I pathway was blocked. Overall, our results suggest that cellular HB antagonizes CSFV growth and replication by triggering IFN signaling, and might represent a novel antiviral restriction factor. This study reports for the first time the novel role of HB in innate immunity.
KW - Animals
KW - Capsid Proteins
KW - Cell Line
KW - Centrifugation
KW - Classical swine fever virus
KW - Flaviviridae
KW - Hemoglobins
KW - Host-Pathogen Interactions
KW - Humans
KW - Immunoprecipitation
KW - Mass Spectrometry
KW - Microscopy, Confocal
KW - Pestivirus
KW - Protein Binding
KW - Protein Interaction Mapping
KW - Protein Subunits
KW - Swine
KW - Virus Assembly
KW - Virus Replication
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1128/JVI.03130-12
DO - 10.1128/JVI.03130-12
M3 - Journal article
C2 - 23487454
VL - 87
SP - 5707
EP - 5717
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 10
ER -