13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Herpesviruses dUTPases: A New Family of Pathogen-Associated Molecular Pattern (PAMP) Proteins with Implications for Human Disease

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The human herpesviruses are ubiquitous viruses and have a prevalence of over 90% in the adult population. Following a primary infection they establish latency and can be reactivated over a person’s lifetime. While it is well accepted that human herpesviruses are implicated in numerous diseases ranging from dermatological and autoimmune disease to cancer, the role of lytic proteins in the pathophysiology of herpesvirus-associated diseases remains largely understudies. Only recently have we begun to appreciate the importance of lytic proteins produced during reactivation of the virus, in particular the deoxyuridine triphosphate nucleotidohydrolases (dUTPase), as key modulators of the host innate and adaptive immune responses. In this review, we provide evidence from animal and human studies of the Epstein–Barr virus as a prototype, supporting the notion that herpesviruses dUTPases are a family of proteins with unique immunoregulatory functions that can alter the inflammatory microenvironment and thus exacerbate the immune pathology of herpesvirus-related diseases including myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune diseases, and cancer.

          Related collections

          Most cited references164

          • Record: found
          • Abstract: found
          • Article: not found

          The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.

          Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain-Barré syndrome. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Inferences, questions and possibilities in Toll-like receptor signalling.

            The Toll-like receptors (TLRs) are the key proteins that allow mammals--whether immunologically naive or experienced--to detect microbes. They lie at the core of our inherited resistance to disease, initiating most of the phenomena that occur in the course of infection. Quasi-infectious stimuli that have been used for decades to study inflammatory mechanisms can activate the TLR family of proteins. And it now seems that many inflammatory processes, both sterile and infectious, may depend on TLR signalling. We are in a good position to apply our understanding of TLR signalling to a range of challenges in immunology and medicine.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The pathogenesis of lupus nephritis.

              Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                28 December 2016
                March 2017
                : 6
                : 1
                : 2
                Affiliations
                [1 ]Department of Cancer Biology and Genetics, Wexner Medical Center, Ohio State University, Columbus, OH 43210, USA; Williams.70@ 123456osu.edu
                [2 ]Institute for Behavioral Medicine Research, Ohio State University, Columbus, OH 43210, USA; Brandon.Cox@ 123456osumc.edu
                Author notes
                [* ]Correspondence: maria.ariza@ 123456osumc.edu ; Tel.: +1-614-366-3065; Fax: +1-614-366-2097
                Article
                pathogens-06-00002
                10.3390/pathogens6010002
                5371890
                28036046
                d70a6cdc-88a3-4d93-96a4-faf0adde6674
                © 2016 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 December 2016
                : 21 December 2016
                Categories
                Review

                herpesviruses,epstein–barr virus,deoxyuridine triphosphate nucleotidohydrolase,toll-like receptor 2,myalgic encephalomyelitis/chronic fatigue syndrome,autoimmune diseases,lupus nephritis,cancer

                Comments

                Comment on this article