Herpesvirus saimiri vFLIP provides an antiapoptotic function but is not essential for viral replication, transformation, or pathogenicity.
Apoptosis of infected cells is an important host defense mechanism, and many viruses have exploited antiapoptotic proteins that interfere with crucial cellular pathways. Viral FLICE inhibitory proteins (vFLIPs) are encoded by rhadinoviruses like herpesvirus saimiri, the related Kaposi's sarcoma-associated herpesvirus-human herpesvirus 8 (KSHV/HHV8), and the poxvirus responsible for molluscum contagiosum. The vFLIPs can block the interaction of the death receptor-adapter complex with the cellular effector FLICE (caspase-8), and this prevents the initiation of the downstream caspase cascade. KSHV/HHV8 vFLIP overexpression can confer resistance to T-cell-mediated apoptosis and acts as a tumor progression factor in a murine B-cell lymphoma model. To analyze the function of herpesvirus vFLIPs in the genetic background of the virus and in a model for viral pathogenesis, we deleted the vFLIP gene (open reading frame 71) from the genome of herpesvirus saimiri strain C488. The viral deletion mutant was viable and replicated like the wild-type virus. An antiapoptotic effect could be attributed to the vFLIP gene, but we also show that the vFLIP gene of herpesvirus saimiri is dispensable for viral transformation of T cells in vitro and for pathogenicity in cottontop tamarins in vivo.
Glykofrydes
D
D
Institut für Klinische und Molekulare Virologie der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Niphuis
H
H
Kuhn
E M
EM
Rosenwirth
B
B
Heeney
J L
JL
Bruder
J
J
Niedobitek
G
G
Müller-Fleckenstein
I
I
Fleckenstein
B
B
Ensser
A
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000821:virology*; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D011995:Recombination, Genetic; D014412:Tumor Virus Infections / Q000821:virology*; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics
D061945:Caspase Inhibitors; D014764:Viral Proteins; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases