Toll-like receptor sensing of human herpesvirus infection

Abstract

Toll-like receptors (TLRs) are evolutionarily conserved pathogen sensors that constitute the first line of defense in the human immune system. Herpesviruses are prevalent throughout the world and cause significant disease in the human population. Sensing of herpesviruses via TLRs has only been documented in the last 10 years and our understanding of the relationship between these sentinels of the immune system and herpesvirus infection has already provided great insight into how the host cell responds to viral infection. This report will summarize the activation and modulation of TLR signaling in the context of human herpesvirus infections.

Keywords: TLR; cytokines; herpesvirus; innate immunity; interferons.

Figure 1

Human herpesviruses can stimulate a wide variety of TLRs leading to upregulation of both inflammatory cytokines and type I interferon. (A) Activation of NF-κB and inflammatory cytokines (IL-6, IL-8, and IL-12) via TLR stimulation by human herpesviruses. TLR stimulation results in activation of NF-κB in the cytoplasm and subsequent translocation to the nucleus where it serves as a transcriptional activator for a large number of inflammatory cytokines. Activation of these cytokines can occur after stimulation of both endosomal and cell surface TLRs by human herpesviruses. (B) Activation of type I interferon in response to recognition of human herpesviruses by TLRs. Both IFN-α and IFN-β are activated by cellular interferon regulatory factors (IRFs), specifically IRF3 and IRF7, which translocate to the nucleus following phosphorylation and activate the IFN-α and IFN-β promoters. Activation of type I interferon are induced after stimulation of both cell surface TLRs (TLR2 and TLR4), and endosomal TLRs (TLR3, 7, and 9).