Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship
Figure 1
Activation and viral-induced modulation of early phases, HCMV attachment, entry, and intracellular phases of the viral cycle. (a) The binding of viral glycoprotein B (gB) induces the release of type I interferons (IFN) via IFN regulatory factor (IRF) 3, whereas contact between viral glycoproteins gB and gH and toll-like receptor (TLR)2 induces the activation of NF-κB and the release of proinflammatory cytokines. Expression of the intracellular receptor retinoic acid-inducible gene I (RIG-I) is also upregulated in the early phases, the DNA sensor DNA-dependent activator of IFN-regulatory factors (DAI) is activated, triggering IRF-3 activation and type I IFN production. (b) After viral entry, HCMV immunoevasion strategies are activated. Virion-associated and newly produced pp65 prevents IRF3 activation and subsequently impairs the production of type I IFN. Viral pp65 also inhibits NF-κB activation. RIG-I is downmodulated by an unknown mechanism, likely contributing to reduced IFN production. +; upregulation or activation, −; downmodulation or inhibition.
