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Intrinsic Immunity pp 229–257Cite as

Interplay Between DNA Tumor Viruses and the Host DNA Damage Response

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 371))

Abstract

Viruses encounter many challenges within host cells in order to replicate their nucleic acid. In the case of DNA viruses, one challenge that must be overcome is recognition of viral DNA structures by the host DNA damage response (DDR) machinery. This is accomplished in elegant and unique ways by different viruses as each has specific needs and sensitivities dependent on its life cycle. In this review, we focus on three DNA tumor viruses and their interactions with the DDR. The viruses Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) account for nearly all of the virus-associated human cancers worldwide. These viruses have also been excellent models for the study of oncogenic virus-mediated cell transformation. In this review, we will discuss how each of these viruses engage and subvert aspects of the host DDR. The first level of DDR engagement is a result of the genetic linkage between the oncogenic potential of these viruses and their ability to replicate. Namely, the promotion of cells from quiescence into the cell cycle to facilitate virus replication can be sensed through aberrant cellular DNA replication structures which activate the DDR and hinder cell transformation. DNA tumor viruses subvert this growth-suppressive DDR through changes in viral oncoprotein expression which ultimately facilitate virus replication. An additional level of DDR engagement is through direct detection of replicating viral DNA. These interactions parallel those observed in other DNA virus systems in that the need to subvert these intrinsic sensors of aberrant DNA structure in order to replicate must be in place. DNA tumor viruses are no exception. This review will cover the molecular features of DNA tumor virus interactions with the host DDR and the consequences for virus replication.

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Abbreviations

DDR:

DNA damage response

EBV:

Epstein-Barr virus

KSHV:

Kaposi’s sarcoma-associated herpesvirus

HPV:

Human papillomavirus

ATM:

Ataxia-telangiectasia mutated

ATR:

Ataxia-telangiectasia and RAD3-related

MRN:

Mre11-Rad50-Nbs1

BL:

Burkitt’s lymphoma

LCL:

Lymphoblastoid cell line

DSB:

Double-stranded break

ssDNA:

Single-stranded DNA

EBNA:

Epstein-Barr virus nuclear antigen

LMP:

(EBV) latent membrane protein

vFLIP:

(KSHV) viral FLICE (FADD-like IL-1β-converting enzyme) inhibitory protein

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Acknowledgments

This publication resulted (in part) from research supported by the Duke University Center for AIDS Research (CFAR), an NIH funded program (5P30 AI064518); as well as an NIH funded R01 (R01-CA140337); a Viral Oncology Training grant (VOTG: T32-CA009111) and IRTPA Training grant (T32-AI007392). We would also like to thank members of the Luftig lab for helpful discussions.

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  1. Department of Molecular Genetics and Microbiology, Center for Virology, Duke University Medical Center, Durham, NC, 27710, USA

    Karyn McFadden & Micah A. Luftig

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  1. Karyn McFadden
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  2. Micah A. Luftig
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Correspondence to Micah A. Luftig .

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  1. Center for Virology, Department of Molecular Genetics and Mic, Duke University Medical Center, Research Drive 213, Durham, 27710, North Carolina, USA

    Bryan R. Cullen

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McFadden, K., Luftig, M.A. (2013). Interplay Between DNA Tumor Viruses and the Host DNA Damage Response. In: Cullen, B. (eds) Intrinsic Immunity. Current Topics in Microbiology and Immunology, vol 371. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37765-5_9

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