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Description

Human herpesvirus-8 (also known as Kaposi's sarcoma-associated herpesvirus, HHV-8, KSHV) is etiologically associated with all forms of Kaposi sarcoma (KS) including classic, endemic, transplant-related, and AIDS-related, as well as rare neoplastic disorders. It is a double stranded DNA virus with a large genome that encodes for over 87 open reading frames (ORFs) including genes necessary for capsid, tegument, envelope, DNA replication and regulatory proteins. HHV-8 undergoes a bi-phasic lifecycle and can persist indefinitely in the infected host in a latent form during which time only a small fraction of regulatory viral proteins is expressed. ORF45 is an immediate-early phosphoprotein that localizes in the cytoplasm and acts as a viral lytic protein. It interacts with KIF3A, a subunit of kinesin-2 motor protein that transports cargoes along microtubules to cell periphery. The N-terminal amino acids 1-115 and C-terminal amino acids 332-407 of ORF45 are reported to interact with KIF3A. Inhibition of KIF3A-ORF45 interaction is shown to reduce HHV-8 maturation and egress. ORF45 also interacts with interferon regulatory factor 7 and inhibits virus-mediated interferon a/b induction. (Ref.: Sathish, N., et al. (2009). PLoS Pathog 5(3): e1000332, Zhu, FX., et al. (2005). J. Virol. 79(2),800-811, Zhu, FX., and Yuan, Y. (2003). J. Virol. 77(7), 4221-4230).