The latency protein LANA2 from Kaposi's sarcoma-associated herpesvirus inhibits apoptosis induced by dsRNA-activated protein kinase but not RNase L activation.
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.
Esteban
M
M
Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
García
M A
MA
Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Domingo-Gil
E
E
Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Arroyo
J
J
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal sn, 28040 Madrid, Spain.
Nombela
C
C
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal sn, 28040 Madrid, Spain.
Rivas
C
C
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal sn, 28040 Madrid, Spain.
D015088:2',5'-Oligoadenylate Synthetase / Q000502:physiology; D000818:Animals; D000956:Antigens, Viral; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D004722:Endoribonucleases / Q000502:physiology*; D004789:Enzyme Activation; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007372:Interferons / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics; D019892:eIF-2 Kinase / Q000502:physiology*
D000956:Antigens, Viral; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C109540:latency-associated nuclear antigen; D007372:Interferons; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases