mitochondrial DNA antiviral

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1-4 . The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5 . Patients homozygous for the MIRAS variant p...

PrimPol is a human DNA primase-polymerase which restarts DNA synthesis beyond DNA lesions and non-B DNA structures blocking replication. Disfunction of PrimPol in cells leads to slowing of DNA replication rates in mitochondria and nucleus, accumulation of chromosome aberrations, cell cycle delay, and elevated sensitivity to DNA-damaging agents. A defective PrimPol has been suggested to be associated with the development of ophthalmic diseases, elevated mitochondrial toxicity of antiviral drugs and increased cell resistance to chemotherapy...

Previous studies have shown that interferon gene-stimulating protein (STING) is essential for IFN-γ-inducible protein 16 (IFI16) as the DNA sensor and RNA sensor to induce transcription of type I interferon (IFN-I) and is essential for IFI16 to synergize with DNA sensor GMP-AMP (cGAMP) synthase (cGAS) in induction of IFN-I transcription. While other and our previous studies have shown that IFI16 enhanced retinoic acid-inducible gene I (RIG-I)-, which was an RNA sensor, and mitochondrial antiviral signaling (MAVS)-, which was the adaptor protein of RIG-I, induced production of IFN-I, so we wonder whether IFI16 regulates the signal pathway of RNA-RIG-I-MAVS-IFN-I in a STING-dependent manner...

UNLABELLED: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus with high pathogenicity. There has been a gradual increase in the number of reported cases in recent years, with high morbidity and mortality rates. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays an important role in the innate immune defense activated by viral infection; however, the role of the cGAS-STING signaling pathway during SFTSV infection is still unclear...

BACKGROUND: β-d-N4-Hydroxycytidine (NHC) is the active metabolite of molnupiravir, a broad-spectrum antiviral approved by the MHRA for COVID-19 treatment. NHC induces lethal mutagenesis of the SARS-CoV-2 virus, undergoing incorporation into the viral genome and arresting viral replication. It has previously been reported that several nucleoside analogues elicit off-target inhibition of mitochondrial DNA (mtDNA) or RNA replication. Although NHC does not exert these effects in HepG2 cells, HepaRG are proven to be advantageous over HepG2 for modelling nucleoside analogue-induced mitochondrial dysfunction...

The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay...

Hepatitis B virus (HBV) infection is a serious global health problem. After the viruses infect the human body, the host can respond to the virus infection by coordinating various cellular responses, in which mitochondria play an important role. Evidence has shown that mitochondrial proteins are involved in host antiviral responses. In this study, we found that the overexpression of TIM22 and TIM29, the members of the inner membrane translocase TIM22 complex, significantly reduced the level of intracellular HBV DNA and RNA and secreted HBV surface antigens and E antigen...

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling and apoptosis. Recent studies have shown that mitochondria play an important role in other pathophysiological functions in addition to cellular energy metabolism. Mitochondria release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) to activate Toll-like receptor 9 (TLR9), NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune signaling pathways against foreign pathogenic microorganisms...

The enzyme cyclic GMP-AMP synthase (cGAS) is a key sensor for detecting misplaced double-stranded DNA (dsDNA) of genomic, mitochondrial, and microbial origin. It synthesizes 2'3'-cGAMP, which in turn activates the stimulator of interferon genes pathway, leading to the initiation of innate immune responses. Here, we identified Listerin as a negative regulator of cGAS-mediated innate immune response. We found that Listerin interacts with cGAS on endosomes and promotes its K63-linked ubiquitination through recruitment of the E3 ligase TRIM27...

BACKGROUND: The objective of this study was to evaluate the effects of glutamine on the growth performance and systemic innate immune response in broiler chickens challenged with Salmonella pullorum. A total of 600 one-day-old Arbor Acres broiler chickens were assigned randomly to 6 dietary treatments with 10 replicates for a 21-day feeding experiment. The experimental treatments were as follows: the control treatment (birds fed the basal diet), the Gln1 treatment, and the Gln 2 treatment (birds fed the basal diet supplemented with 0...

Protease activated receptors (PARs) are cleaved by coagulation proteases and thereby connect hemostasis with innate immune responses. Signaling of the tissue factor (TF) complex with FVIIa via PAR2 stimulates extracellular signal-regulated kinase (ERK) activation and cancer cell migration, but functions of cell autonomous TF-FVIIa signaling in immune cells are unknown. Here we show that myeloid cell expression of FVII but not of FX is crucial for inflammatory cell recruitment to the alveolar space after challenge with the double stranded viral RNA mimic Poly(I:C)...

The stimulator of interferon genes (STING) is a crucial signaling hub in the immune system's antiviral and antimicrobial defense by detecting exogenous and endogenous DNA. The multifaceted functions of STING have been uncovered gradually during past decades, including homeostasis maintenance and overfull immunity or inflammation induction. However, the subcellular regulation of STING and mitochondria is poorly understood. The main functions of STING are outlined in this review. Moreover, we discuss how mitochondria and STING interact through multiple mechanisms, including the release of mitochondrial DNA (mtDNA), modulation of mitochondria-associated membrane (MAM) and mitochondrial dynamics, alterations in mitochondrial metabolism, regulation of reactive oxygen species (ROS) production, and mitochondria-related cell death...

Poxviruses are unusual DNA viruses that replicate in the cytoplasm. To do so, they encode approximately 100 immunomodulatory proteins that counteract cytosolic nucleic acid sensors such as cGAMP synthase (cGAS) along with several other antiviral response pathways. Yet most of these immunomodulators are expressed very early in infection while many are variable host range determinants, and significant gaps remain in our understanding of poxvirus sensing and evasion strategies. Here, we show that after infection is established, subsequent progression of the viral lifecycle is sensed through specific changes to mitochondria that coordinate distinct aspects of the antiviral response...

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months...

Molluscum contagiosum virus (MCV) is a poxvirus that causes benign, persistent skin lesions. MCV encodes a variety of immune evasion molecules to dampen host immune responses. Two of these proteins are the MC159 and MC160 proteins. Both MC159 and MC160 contain two tandem death effector domains and share homology to the cellular FLIPs, FADD, and procaspase-8. MC159 and MC160 dampen several innate immune responses such as NF-κB activation and mitochondrial antiviral signaling (MAVS)-mediated induction of type 1 interferon (IFN)...

Hepatitis C virus (HCV) infection can regulate the number and dynamics of mitochondria, and is associated with a prominent hepatic mitochondrial injury. Mitochondrial distress conveys oxidative damage which is implicated in liver disease progression. The present study was conducted to assess the change of mitochondrial DNA (mtDNA) copy number in patients with HCV-related chronic liver disease and the impact of direct-acting antiviral (DAA) therapy. Whole blood mtDNA copy number was measured using real-time quantitative polymerase chain reaction at baseline and 12 weeks after the end of therapy in 50 treatment-naïve HCV-infected patients who achieved sustained viral response (SVR) after DAA therapy and 20 healthy controls...

Mitochondrial antiviral signaling protein (MAVS) and stimulator of interferon (IFN) genes (STING) are crucial factors of IFN induction in RNA and DNA viral infections. However, unrestricted IFN was harmful to the host by causing cytokine storm. Here, we report that zebrafish transmembrane protein 47 (TMEM47), an IFN-negative regulator in fish, represses IFN expression stimulated by both spring viremia of carp virus (SVCV) and cyprinid herpesvirus 2, which represent RNA and DNA viruses, respectively. The mRNA level of tmem47 was rapidly upregulated during RNA and DNA virus infection...

Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus that replicates well in mosquito, bird, and mammalian cells. An in vivo study revealed that BALB/c mice and Kunming mice were susceptible to DTMUV after intracerebral inoculation. Moreover, there are no reports about DTMUV-related human disease, but antibodies against DTMUV and viral RNA were detected in the serum samples of duck industry workers. This information implies that DTMUV has expanded its host range and poses a threat to mammalian health...

INTRODUCTION: Since the beginning of the COVID-19 pandemic, a wide clinical spectrum, from asymptomatic infection to mild or severe disease and death, have been reported in COVID-19 patients. Studies have suggested several possible factors, which may affect the clinical outcome of COVID-19. A pro-inflammatory state and impaired antiviral response have been suggested as major contributing factors in severe COVID-19. Considering that mitochondria have an important role in regulating the immune responses to pathogens, pro-inflammatory signaling, and cell death, it has received much attention in SARS-CoV-2 infection...

OBJECTIVE: Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism. DESIGN: In total, 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, were recruited for this study...