Diverse mechanisms evolved by DNA viruses to inhibit early host defenses

Marni S. Crow, Krystal K. Lum, Xinlei Sheng, Bokai Song, Ileana M. Cristea

Research output: Contribution to journalReview article

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)452-481
Number of pages30
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume51
Issue number6
DOIs
StatePublished - Nov 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Keywords

  • Viral immune evasion
  • apoptosis
  • innate immunity
  • intrinsic immunity
  • post-translational modification
  • proteasomal degradation
  • viral mimicry
  • virus–host interactions

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