Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) uses several strategies to counteract the interferon (IFN) system. In this study, the relationship of the protein LANA2 from KSHV to the IFN-activated protein kinase (PKR) and 2-5A system was analysed. It was found that LANA2 could not abrogate apoptosis or RNA degradation mediated by the 2-5A system. However, expression of LANA2 inhibited apoptosis triggered by PKR. LANA2 also counteracted the PKR-mediated inhibition of protein synthesis and partially blocked PKR-induced phosphorylation of eIF-2alpha. Analysis of PKR-induced activation of caspases 3 and 9 revealed that LANA2 abrogated activation of caspase 3 but not of caspase 9. These findings show that LANA2 is able to interfere with downstream events triggered by PKR. Hence, LANA2 should be considered as a KSHV defence protein against IFN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2',5'-Oligoadenylate Synthetase / physiology
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Animals
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Antigens, Viral
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Apoptosis / physiology
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Caspase 3
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Caspase 9
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Caspases / metabolism
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Cell Line
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Chlorocebus aethiops
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Endoribonucleases / physiology*
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Enzyme Activation
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Herpesvirus 8, Human / genetics
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Herpesvirus 8, Human / immunology
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Herpesvirus 8, Human / physiology*
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Interferons / physiology
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Mice
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Protein Biosynthesis
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Recombinant Proteins / genetics
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Vaccinia virus / genetics
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eIF-2 Kinase / physiology*
Substances
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Antigens, Viral
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Nuclear Proteins
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Recombinant Proteins
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latency-associated nuclear antigen
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Interferons
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eIF-2 Kinase
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2',5'-Oligoadenylate Synthetase
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Endoribonucleases
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2-5A-dependent ribonuclease
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CASP3 protein, human
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CASP9 protein, human
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Casp3 protein, mouse
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Casp9 protein, mouse
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Caspase 3
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Caspase 9
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Caspases