title: Poor growth of human adenovirus-12 compared to adenovirus-2 correlates with a failure to impair PKR activation during the late phase of infection.
abstract: Human adenovirus type 12 (HAdV-12) displays a relatively low virulence and slow replication in cultured human cells, which is manifested by premature death of HAdV-12-infected cells. Whereas HAdV-2 induction of IFN-β expression was transient, HAdV-12-infected cells maintained high levels of IFN-β expression, protein kinase R (PKR) activation and eIF-2α phosphorylation throughout the infectious cycle. The importance of the IFN-inducible PKR kinase in restriction of HAdV-12 was supported by the enhanced growth of the virus following PKR knockdown in HeLa cells. Ectopic expression of HAdV-2 VA RNAI increased HAdV-12 hexon protein expression, suggesting that insufficient VA RNA expression contributes to the restricted growth of HAdV-12. Although some adenovirus species are known to persist in human lymphoid tissues, HAdV12 has so far not been found. Thus, it is possible that the inability of HAdV12 to evade the INF response may have implications for the virus to establish long-lasting or persistent infections.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Lufeng
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Samuel
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Akusjärvi
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden. Electronic address: Catharina.Svensson@imbim.uu.se.
authors.forename: Catharina
authors.initials: C
authors.lastname: Svensson
mesh_terms: D000260:Adenoviruses, Human / Q000145:classification / Q000201:enzymology / Q000254:growth & development*; D016923:Cell Death; D002460:Cell Line; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D007372:Interferons; D010766:Phosphorylation; D014779:Virus Replication / Q000502:physiology*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D007372:Interferons; D019892:eIF-2 Kinase
keywords: Adenovirus; IFN; PKR; VA RNA; eIF2α