Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
DOI: 10.1017/S1462399406010544; 6 March 2006
Alison Sinclair, Sarah Yarranton and Celine Schelcher (2006) DNA-damage response pathways triggered by viral replication.
Expert Rev. Mol. Med. Vol. 8, Issue 5, DOI: 10.1017/S1462399406010544

DNA-damage response pathways triggered by viral replication

Alison Sinclair, Sarah Yarranton and Celine Schelcher

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Many viruses, with distinct replication strategies, activate DNA-damage response pathways, including the lentivirus human immunodeficiency virus (HIV) and the DNA viruses Epstein–Barr virus (EBV), herpes simplex virus 1, adenovirus and SV40. DNA-damage response pathways involving DNA-dependent protein kinase, ataxia-telengiectasia mutated (ATM) and ‘ataxia-telengiectasia and Rad3-related’ (ATR) have all been implicated. This review focuses on the effects of HIV and EBV replication on DNA repair pathways. It has been suggested that activation of cellular DNA repair and recombination enzymes is beneficial for viral replication, as illustrated by the ability of suppressors of the ATM and ATR family to inhibit HIV replication. However, activation of DNA-damage response pathways can also promote apoptosis. Viruses can tailor the cellular response by suppressing downstream signalling from DNA-damage sensors, as exemplified by EBV. New small-molecule inhibitors of the DNA-damage response pathways could therefore be of value to treat viral infections.

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Figure 1. Overview of the transition of the retroviral genome from ss RNA to integrated ds DNA.
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Figure 2. Overview of lytic replication of the Epstein–Barr virus genome.
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Table 1. Overview of the components of the DNA damage responses to single-strand and double-strand breaks
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