Diverse mechanisms evolved by DNA viruses to inhibit early host defenses

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 upon 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.

Host–transposon interactions: conflict, cooperation, and cooption

“…Consistent with this quandary, all TE-encoded antisilencing mechanisms described thus far have narrow effects or modes of action either resulting in modest decreases of host regulatory proteins (mir820 and Athila6 tasiRNA) or selectively targeting individual families (VANC). This is in stark contrast to viruses, which evolve mechanisms that achieve broad and/or highly effective blocks of the targeted pathways (Crow et al 2016;Hynes et al 2018;Landsberger et al 2018).…”

“…The dearth of antisilencing strategies described in eukaryotic TEs is all the more surprising given the plethora of strategies described for viruses and other pathogens to counteract host defense mechanisms. These include many examples of virus-encoded proteins that directly antagonize or degrade host defense systems, such as RNAi, CRISPR, and nucleic acid sensors to name just a few (for review, see Crow et al 2016;Hynes et al 2018;Landsberger et al 2018).…”

Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome

“…Eukaryotic DNA and RNA viruses broadly use virally encoded ribonucleases to globally degrade host transcripts in the infected cell, which sabotage their hosts through modulation of transcript and protein levels. This decrease in transcript abundance leads to a downregulation of innate immune responses, processes which are detrimental to the host but are ultimately reversable (Crow et al 2016; Rivas et al 2016). Conversely, degradation of the host chromosome is a host takeover process that is unique to phages.…”

Mono-ADP-ribosylation by ARTD10 restricts Chikungunya virus replication by interfering with the proteolytic activity of nsP2

“…Viruses have developed multifaceted strategies to evade or even hijack cellular mechanisms, e.g. encoding proteins that regulate PTMs and thereby counteract the antiviral reaction of the host [1–5]. Recent findings have elaborated on the role of intracellular ADP-ribosylation at the host-pathogen interface [6–12].…”