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The Role of Gammaherpesviruses in Cancer Pathogenesis

Department of Microbiology and Tumor Virology Program, Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610, Hamilton Walk, Philadelphia, PA 19104, USA
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Author to whom correspondence should be addressed.
These authors contributed equally.
Pathogens 2016, 5(1), 18; https://doi.org/10.3390/pathogens5010018
Received: 10 December 2015 / Accepted: 27 January 2016 / Published: 6 February 2016
(This article belongs to the Special Issue Viral Pathogenesis)
Worldwide, one fifth of cancers in the population are associated with viral infections. Among them, gammaherpesvirus, specifically HHV4 (EBV) and HHV8 (KSHV), are two oncogenic viral agents associated with a large number of human malignancies. In this review, we summarize the current understanding of the molecular mechanisms related to EBV and KSHV infection and their ability to induce cellular transformation. We describe their strategies for manipulating major cellular systems through the utilization of cell cycle, apoptosis, immune modulation, epigenetic modification, and altered signal transduction pathways, including NF-kB, Notch, Wnt, MAPK, TLR, etc. We also discuss the important EBV latent antigens, namely EBNA1, EBNA2, EBNA3’s and LMP’s, which are important for targeting these major cellular pathways. KSHV infection progresses through the engagement of the activities of the major latent proteins LANA, v-FLIP and v-Cyclin, and the lytic replication and transcription activator (RTA). This review is a current, comprehensive approach that describes an in-depth understanding of gammaherpes viral encoded gene manipulation of the host system through targeting important biological processes in viral-associated cancers. View Full-Text
Keywords: EBV; KSHV; cancer; pathogenesis; epigenetics; apoptosis; autophagy; cell cycle; LANA; EBNA3C EBV; KSHV; cancer; pathogenesis; epigenetics; apoptosis; autophagy; cell cycle; LANA; EBNA3C
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Jha, H.C.; Banerjee, S.; Robertson, E.S. The Role of Gammaherpesviruses in Cancer Pathogenesis. Pathogens 2016, 5, 18.

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