A circadian model for viral persistence.

Abstract:

:Persistently infecting DNA viruses depend heavily on host cell DNA synthesis machinery. Replication of cellular and viral DNA is inhibited by mutagenic stress. It is hypothesized that diurnal regulation of viral DNA replication may occur at the level of cell cycle checkpoints and DNA repair, to protect DNA from exposure to UV light or other mutagens. This highly conserved mechanism is traced back to viruses that persist in prokaryotes and eukaryotes. Inhibition of viral DNA replication and the cell cycle in response to UV light may represent a functional building block in the evolution of circadian-gated DNA replication. Viral DNA replication appears to be closely linked to the circadian clock by interaction of viral promoters, early viral proteins and transcription factors. It is proposed here that under certain conditions viral oncogene expression is phase-shifted relative to that of tumor suppressor and DNA repair genes. The resulting desynchrony of checkpoint controls and DNA repair from diurnal genotoxic exposure produces cyclic periods of suboptimal response to DNA damage. This temporal vulnerability to genotoxic stress produces a "mutator phenotype" with inherent genome instability. The proposed model delineates areas of research with implications for viral pathogenesis and therapeutics.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Shadan FF

doi

10.1016/j.mehy.2006.08.018

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

546-53

issue

3

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(06)00612-8

journal_volume

68

pub_type

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