Recognition of herpesviruses by the innate immune system, 2011, Paludan et al.

Recognition of herpesviruses by the innate immune system
Paludan, Søren R.; Bowie, Andrew G.; Horan, Kristy A.; Fitzgerald, Katherine A.

Advances in innate immunity over the past decade have revealed distinct classes of pattern recognition receptors (PRRs) that detect pathogens at the cell surface and in intracellular compartments. This has shed light on how herpesviruses, which are large disease-causing DNA viruses that replicate in the nucleus, are initially recognized during cellular infection. Surprisingly, this involves multiple PRRs both on the cell surface and within endosomes and the cytosol.

In this article we describe recent advances in our understanding of innate detection of herpesviruses, how this innate detection translates into anti-herpesvirus host defence, and how the viruses seek to evade this innate detection to establish persistent infections.

Link | PDF | (Nature Reviews Immunology, Paywall*)

 

Key Points —

Herpesviruses are a large family of DNA viruses, eight of which can cause diseases in humans, particularly in children and immunocompromised individuals. All herpesviruses have the capacity to cause lytic infection in permissive cells and to establish latent or recurrent infections in other cell types.

The innate immune system detects infections using germline-encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are membrane-bound PRRs that detect microorganisms in extracellular and endosomal locations. TLR2, TLR3 and TLR9 are well-described sensors of herpesvirus infections.

In the cytoplasm, active innate immune surveillance takes place and is mediated by nucleic acid sensors. Herpesvirus infections are sensed by both RNA and DNA sensing systems, and recent reports suggest a particularly important role for the cytosolic DNA-sensing AIM2-like receptor (ALR) family in intracellular detection of herpesviruses.

Given the relatively slow replication cycle of herpesviruses and the establishment of life-long infections, these viruses are highly dependent on efficient immune evasion strategies. It is now known that herpesviruses evade all classes of PRRs (including ALRs), as well as the downstream signalling machinery.

Innate immune defence against herpesviruses is highly dependent on the type I interferon system and natural killer cells. Model studies in mice and genetic data from humans have revealed essential roles for both TLRs and intracellular DNA sensors in mounting protective immune responses against herpesviruses.