About this Research Topic
The interplay between Herpesviruses and the early innate immune response is a critical process that determines the development of the adaptive immune response and eventually the outcome of the infection. The emerging picture in antiviral immunology is that the early antiviral immune response against herpesviruses, and viruses in general, consist of at least three arms, which fundamentally differ from each other in many respects, including time of action relative to infection and the molecular mechanisms that mediate their functional activity.
The first arm comprises the so-called “Restriction Factors”. Such intrinsic immune mechanisms are highly important as they provide an antiviral frontline defense mediated by constitutively expressed proteins, already present and ready for activity before a virus enters a cell. These intrinsic immune mechanisms were initially discovered as being active against retroviruses and involve the APOBEC3 class of cytidine deaminases, a large family of proteins termed the TRIM family, and tetherin, an interferon-inducible protein, which blocks the release of HIV-1. Emerging evidence, however, indicate that such intrinsic immune mechanisms are also active against other viruses, including Herpesviruses, Vesicular Stomatitis Virus, Filoviruses, Influenza Virus, and Hepatitis C Virus, and are more numerous and target-specific than previously thought.
The second arm of the early antiviral response is based on pattern recognition receptors (PRR). Upon recognition of foreign structures, such as microbial nucleic acids, the PRR activate intracellular signaling, most notably one triggers the production of antiviral interferons (IFNs), and a second one that leads to the assembly of the inflammasome, which in turn promotes the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). Type I IFNs are important for control of herpesvirus infections, since mutations in genes encoding IFN-inducing proteins are susceptible to encephalitis caused by herpesviruses.
The third arm of the early immune response is contributed by the Natural killer (NK) cells and cells of myeloid origin, including macrophages and Dendritic Cells (DC), which are able to kill virus-infected cells without the requirement for previous exposure to the pathogen. Moreover, NK cells produce different important cytokines which stimulate the antiviral adaptive immune response, particularly IFN. NK cells are very important for control of herpesvirus infections, as demonstrated by the systemic and life-threatening Herpesvirus disease symptoms in patients with deficiencies in NK cell activity, and by the several strategies exploited by Herpesviruses to escape NK cell control.
In this Research Topic, we provide an overall picture of how key players in early immunity act to exert control of herpesvirus infections, and integrate with each other to achieve this. In addition, we will cover the different evasion mechanisms that Herpesviruses have evolved to escape from the host immune surveillance. We believe that the Research Topic will give an updated insight into the vibrant field of herpesvirus immunology, and hope it will serve the purpose to inspire new research activities.
Keywords: Innate Immunity, Herpesviruses, Restriction Factors, Pattern Recognition Receptors, NK cells