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Review
. 2016 Feb 6;5(1):18.
doi: 10.3390/pathogens5010018.

The Role of Gammaherpesviruses in Cancer Pathogenesis

Hem Chandra Jha  1 , Shuvomoy Banerjee  2 , Erle S Robertson  3
Affiliations
Review

The Role of Gammaherpesviruses in Cancer Pathogenesis

Hem Chandra Jha et al. Pathogens. .

Abstract

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.

Keywords: EBNA3C; EBV; KSHV; LANA; apoptosis; autophagy; cancer; cell cycle; epigenetics; pathogenesis.

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Figures

Figure 1
Figure 1
Human tumor associated gammaherpesviruses EBV and KSHV are related to a wide range of human malignancies.
Figure 2
Figure 2
Diagram represents the multi-faceted activities of EBV latent antigen EBNA3C in regulation of DNA damage response, host transcription factors, cell cycle regulatory proteins, cell proliferation and apoptosis during EBV infection.
Figure 3
Figure 3
Schematic shows the vital role of KSHV-latency associated nuclear antigen (LANA)-mediated cancer progression by deregulating DNA damage response, transcription factor activities, and cell proliferation properties.
See this image and copyright information in PMC

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