Kaposi's sarcoma-associated herpesvirus-encoded LANA contributes to viral latent replication by activating phosphorylation of survivin.

[primary effusion lymphoma]

Kaposi 's sarcoma -associated herpesvirus (KSHV ) is a human gammaherpesvirus casually linked to Kaposi 's sarcoma (KS ), multicentric Castleman 's disease (MCD ), and primary effusion lymphoma (PEL ). Previously , we showed that LANA encoded by KSHV upregulates expression of survivin , a member of the inhibitor of apoptosis (IAP ) family . This leads to an increase in the rate of cell proliferation of KSHV-infected B cells . LANA is required for tethering of the KSHV episome to the host chromosomes and efficiently segregates the viral genomes into dividing tumor cells . Here we show that LANA interacts with Aurora kinase B (AK -B ) and induces phosphorylation of survivin at residue T 34 . Phosphorylation of survivin specifically on residue T 34 enhances the activity of p 300 and inhibits the activity of histone deacetylase 1 (HDAC-1 ), which then leads to an increase in acetylation of histone H 3 on the viral genome . Phosphorylation of survivin specifically on residue T 34 upregulates the activities of histone acetyltransferases and deacetylases , which then leads to an increase in viral copy number in KSHV-infected B cells . This results in a boost of KSHV replication in latently infected B-lymphoma cells . The studies showed that LANA can also function to regulate viral replication prior to mitosis of the latently infected cells , suggesting that LANA possesses a novel role in regulating KSHV replication in infected B cells .This work represents a report of KSHV latent protein LANA and its interactions with AK -B leading to induction of phosphorylation of the oncoprotein survivin at residue T 34 . Phosphorylation of survivin specifically on residue T 34 upregulates the activities of histone acetyltransferases and deacetylases . This leads to an increase in viral copy number in KSHV-infected B cells . These studies support a role for LANA in regulating KSHV replication through posttranslation modification in KSHV-infected B cells .