Diverse mechanisms evolved by DNA viruses to inhibit early host defenses.

TitleDiverse mechanisms evolved by DNA viruses to inhibit early host defenses.
Publication TypeJournal Article
Year of Publication2016
AuthorsCrow, MS, Lum, KK, Sheng, X, Song, B, Cristea, IM
JournalCrit Rev Biochem Mol Biol
Date Published2016 Nov/Dec
KeywordsAnimals, Apoptosis, DNA Virus Infections, DNA Viruses, Gene Expression Regulation, Host-Pathogen Interactions, Humans, Immunity, Cellular, Immunity, Innate, Proteasome Endopeptidase Complex, Protein Processing, Post-Translational, Proteolysis, RNA, Messenger, Virus Replication

<p>In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent on the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments.</p>

Alternate JournalCrit Rev Biochem Mol Biol
PubMed ID27650455
PubMed Central IDPMC5285405
Grant ListF31 AI114240 / AI / NIAID NIH HHS / United States
R21 AI102187 / AI / NIAID NIH HHS / United States
R01 GM114141 / GM / NIGMS NIH HHS / United States
R33 AI102187 / AI / NIAID NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States