Herpes Simplex Virus and Pattern Recognition Receptors: An Arms Race

Abstract

Herpes simplex viruses (HSVs) are experts in establishing persistent infection in immune-competent humans, in part by successfully evading immune activation through diverse strategies. Upon HSV infection, host deploys pattern recognition receptors (PRRs) to recognize various HSV-associated molecular patterns and mount antiviral innate immune responses. In this review, we describe recent advances in understanding the contributions of cytosolic PRRs to detect HSV and the direct manipulations on these receptors by HSV-encoded viral proteins as countermeasures. The continuous update and summarization of these mechanisms will deepen our understanding on HSV-host interactions in innate immunity for the development of novel antiviral therapies, vaccines and oncolytic viruses.

Keywords: AIM2; CGAS; DAI; IFI16; PKR; RIG-I/MDA5; herpes simplex virus; pattern recognition receptors.

Figure 1

HSV manipulations on the cytosolic pattern recognition receptors. Viral infection derives molecular patterns (DNAs and RNAs) which activate pattern recognition receptors (light blue) to transduce innate immune signaling through distinct adaptor proteins (blue) and ultimately trigger antiviral responses, including but not limited to cytokine production, inflammasome activation, translational inhibition and necroptosis. To escape innate immune surveillance, HSV encode viral proteins (red) to manipulate multiple steps of each signaling pathway via diverse mechanisms, resulting in a complex HSV-host interaction network on innate immunity.