Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.
Published: July 2020
AI Article Synopsis
Article Abstract
The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA. To initiate signaling, serine 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I interferons (IFNs). Additionally, evolutionary conserved responses such as autophagy also occur downstream of STING, but their relative importance during in vivo infections remains unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) mutation in STING are unexpectedly resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT, suggesting that the STING CTT initiates protective responses against HSV-1, independently of type I IFNs. Interestingly, we find that STING-induced autophagy is a CTT- and TBK1-dependent but IRF3-independent process that is conserved in the STING S365A mice. Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in vivo.
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49 box 1043, Leuven 3000, Belgium.
The widespread use of antivirals in immunocompromised individuals has led to frequent occurrences of drug-resistant herpes simplex virus 1 (HSV-1) infections. Current antivirals target the viral DNA polymerase (DP), resulting in cross-resistance patterns that emphasize the need for novel treatment strategies. In this study, we assessed whether combining antivirals with different targets affects drug resistance emergence by passaging wild-type HSV-1 under increasing concentrations of acyclovir (ACV), foscarnet (phosphonoformic acid, PFA), or the helicase-primase inhibitor pritelivir (PTV), individually or in combination (ACV + PTV or PFA + PTV).
Background: Synthetic CRISPR-Cas9 gene drive has been developed to control harmful species. However, resistance to Cas9 gene drive can be acquired easily when DNA repair mechanisms patch up the genetic insults introduced by Cas9 and incorporate mutations to the sgRNA target. Although many strategies to reduce the occurrence of resistance have been developed so far, they are difficult to implement and not always effective.
Herpes simplex virus type 1 (HSV-1) is a common virus infecting the ocular tissue. It infects eye tissues, such as the eyelid, cornea, and conjunctiva. Corneal HSV-1 infection causes herpes simplex keratitis (HSK), which can induce vision loss.
Herpes simplex virus-1 (HSV-1) is the primary cause of infectious blindness. Despite impressive therapeutic outcomes of conventional treatments, HSV-1 drug resistance can be easily developed. Thus, more constructive strategies should be implemented.
In dentistry, disinfection with antimicrobials is employed under different conditions and at different time points. During the COVID-19 pandemic, the use of disinfectant dental sprays was proposed, among other measures, to help prevent the transmission of infections during dental procedures that require highly effective antiseptics at particularly short contact times. The study aimed to evaluate the efficacy of electrolyzed saline (EOS) compared with other antiseptics in terms of the spread of enveloped and nonenveloped viruses by ultrasonic scaler (USS)-generated dental spray.
