Antiviral activities of ISG20 in positive-strand RNA virus infections

• Published in: Virology (New York, N.Y.) N.Y.), 2011-01, Vol.409 (2), p.175-188
• Main Authors: Zhou, Zhi, Wang, Nan, Woodson, Sara E, Dong, Qingming, Wang, Jie, Liang, Yuqiong, Rijnbrand, Rene, Wei, Lai, Nichols, Joan E, Guo, Ju-Tao, Holbrook, Michael R, Lemon, Stanley M, Li, Kui
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antiviral; Bovine viral diarrhea virus; Cell Line; Exodeoxyribonucleases - genetics; Exodeoxyribonucleases - immunology; Exodeoxyribonucleases - metabolism; Exonucleases - genetics; Exonucleases - immunology; Exonucleases - metabolism; Flavivirus; Hepatitis A virus; Hepatitis C virus; Humans; Infectious Disease; Innate immunity; Interferon; ISG20; ISG20L1; ISG20L2; Molecular Sequence Data; Pestivirus; Picornavirus; RNA Viruses - immunology; RNA Viruses - physiology; RNA, Viral - metabolism; SARS coronavirus; Sequence Alignment; Severe acute respiratory syndrome coronavirus; Viral Load; Viral Plaque Assay; Virus Replication; Yellow fever virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2010.10.008

Abstract ISG20 is an interferon-inducible 3′–5′ exonuclease that inhibits replication of several human and animal RNA viruses. However, the specificities of ISG20's antiviral action remain poorly defined. Here we determine the impact of ectopic expression of ISG20 on replication of several positive-strand RNA viruses from distinct viral families. ISG20 inhibited infections by cell culture-derived hepatitis C virus (HCV) and a pestivirus, bovine viral diarrhea virus and a picornavirus, hepatitis A virus. Moreover, ISG20 demonstrated cell-type specific antiviral activity against yellow fever virus, a classical flavivirus. Overexpression of ISG20, however, did not inhibit propagation of severe acute respiratory syndrome coronavirus, a highly-pathogenic human coronavirus in Huh7.5 cells. The antiviral effects of ISG20 were all dependent on its exonuclease activity. The closely related cellular exonucleases, ISG20L1 and ISG20L2, did not inhibit HCV replication. Together, these data may help better understand the antiviral specificity and action of ISG20.