Mutual Inhibition between Kaposis Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Lytic Replication Initiators in Dually-Infected Primary Effusion LymphomaReport as inadecuate




Mutual Inhibition between Kaposis Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Lytic Replication Initiators in Dually-Infected Primary Effusion Lymphoma - Download this document for free, or read online. Document in PDF available to download.

Background

Both Kaposi-s sarcoma-associated herpesvirus KSHV and Epstein-Barr virus EBV are members of the human gamma herpesvirus family: each is associated with various human cancers. The majority of AIDS-associated primary effusion lymphoma PEL are co-infected with both KSHV and EBV. Dually-infected PELs selectively switch from latency to lytic replication of either KSHV or EBV in response to chemical stimuli. KSHV replication and transcription activator K-RTA is necessary and sufficient for the switch from KSHV latency to lytic replication, while EBV BZLF1 gene product EBV-Z is a critical initiator for induction of EBV lytic replication.

Methodology-Principal Findings

We show K-RTA and EBV-Z are co-localized and physically interact with each other in dually-infected PELs. K-RTA inhibits the EBV lytic replication by nullifying EBV-Z-mediated EBV lytic gene activation. EBV-Z inhibits KSHV lytic gene expression by blocking K-RTA-mediated transactivations. The physical interaction between K-RTA and EBV-Z are required for the mutual inhibition of the two molecules. The leucine heptapeptide repeat LR region in K-RTA and leucine zipper region in EBV-Z are involved in the physical interactions of the two molecules. Finally, initiation of KSHV lytic gene expression is correlated with the reduction of EBV lytic gene expression in the same PEL cells.

Conclusions-Significance

In this report, how the two viruses interact with each other in dually infected PELs is addressed. Our data may provide a possible mechanism for maintaining viral latency and for selective lytic replication in dually infected PELs, i.e., through mutual inhibition of two critical lytic replication initiators. Our data about putative interactions between EBV and KSHV would be applicable to the majority of AIDS-associated PELs and may be relevant to the pathogenesis of PELs.



Author: Yanjun Jiang , Dongsheng Xu , Yong Zhao, Luwen Zhang

Source: http://plos.srce.hr/



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