2022
DOI: 10.3390/biom12020227
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Viral dUTPases: Modulators of Innate Immunity

Abstract: Most free-living organisms encode for a deoxyuridine triphosphate nucleotidohydrolase (dUTPase; EC 3.6.1.23). dUTPases represent a family of metalloenzymes that catalyze the hydrolysis of dUTP to dUMP and pyrophosphate, preventing dUTP from being incorporated into DNA by DNA polymerases, maintaining a low dUTP/dTTP pool ratio and providing a necessary precursor for dTTP biosynthesis. Thus, dUTPases are involved in maintaining genomic integrity by preventing the uracilation of DNA. Many DNA-containing viruses, … Show more

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Cited by 5 publications
(4 citation statements)
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References 136 publications
(169 reference statements)
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“…The escape of these cells from immunosurveillance results in the formation of ectopic EBV latency lymphoid structures in different tissues that promote inflammatory responses by releasing EBERs, producing abortive reactivation and releasing new virions ( 129 133 ). Increased viral reactivation may increase the production of transient autoantibodies and the release of viral dUTPases ( 129 , 134 ). In addition, increased foreign viral antigens from EBV reservoirs, SARS-CoV-2 or vaccine viral vectors, in individuals carrying ancestral HLA class II alleles with the ability to detect a greater number of antigens and activate a greater number of T and B cells, could increase the activation of autoreactive T cells due to their promiscuity and molecular mimicry of self-antigens with viral antigens ( 112 ).…”
Section: Common Model Of Acquired Immunodeficiency and Hypocortisolismmentioning
confidence: 99%
“…The escape of these cells from immunosurveillance results in the formation of ectopic EBV latency lymphoid structures in different tissues that promote inflammatory responses by releasing EBERs, producing abortive reactivation and releasing new virions ( 129 133 ). Increased viral reactivation may increase the production of transient autoantibodies and the release of viral dUTPases ( 129 , 134 ). In addition, increased foreign viral antigens from EBV reservoirs, SARS-CoV-2 or vaccine viral vectors, in individuals carrying ancestral HLA class II alleles with the ability to detect a greater number of antigens and activate a greater number of T and B cells, could increase the activation of autoreactive T cells due to their promiscuity and molecular mimicry of self-antigens with viral antigens ( 112 ).…”
Section: Common Model Of Acquired Immunodeficiency and Hypocortisolismmentioning
confidence: 99%
“…These dUTPases are only expressed during lytic replications or abortive lytic replications and can also increase the secretion of the proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-12, TNF-α, and IFN-γ) and IL-10 (Fig. 1 ) by human dendritic cells, macrophages, and peripheral blood mononuclear cells (PBMC) via TLR2 activation [ 10 , 246 ]. In this way, they also contribute to the chronic innate response and symptomatology.…”
Section: Consequences Of Ebv-acquired Immune Deficiencymentioning
confidence: 99%
“…Therefore, the variety of symptoms will depend on the degree of immunodeficiency present in the individual, the affected tissues, and outbreaks of viral reactivation. In the latter case, the increase in viral reactivation (especially of EBV and Parvovirus B19) or abortive reactivation during periods of increased immunodeficiency may contribute to the exacerbation of symptoms by increasing the production of transient autoantibodies such as ANCAs, causing symptoms of vasculitis [ 241 ], and by increasing the release of viral dUTPases, which increase neurological symptoms [ 246 ].…”
Section: Consequences Of Ebv-acquired Immune Deficiencymentioning
confidence: 99%
“…Based on their oligomerization state, dUTPases can be classified into three families: monomeric [7], homodimeric [8], and homotrimeric [9] enzymes. The homotrimeric family is the largest and includes dUTPases found in various organisms such as plants, animals, fungi, bacteria, and certain viruses like adenoviruses, poxviruses, and retroviruses [10].…”
Section: Introductionmentioning
confidence: 99%