SARS‐CoV‐2 NSP7 inhibits type I and III IFN production by targeting the RIG‐I/MDA5, TRIF, and STING signaling pathways

alexandrossfakianakis shared this article with you from Inoreader SARS‐CoV‐2 NSP7 inhibits type I and III IFN production by targeting the RIG‐I/MDA5, TRIF, and STING signaling pathways via Journal of Medical Virology Abstract SARS-CoV-2 is a poor inducer of innate antiviral immunity, and the underlying mechanism still needs further investigation. Here, we reported that SARS-CoV-2 NSP7 inhibited the production of type I and III IFNs by targeting the RIG-I/MDA5, TLR3-TRIF, and cGAS-STING signaling pathways. SARS-CoV-2 NSP7 suppressed the expression of IFNs and IFN-stimulated genes induced by poly (I:C) transfection and infection with Sendai virus or SARS-CoV-2 virus-like particles. NSP7 impaired type I and III IFN production activated by components of the cytosolic dsRNA-sensing pathway, including RIG-I, MDA5, and MAVS, but not TBK1, IKKε, and IRF3-5D, an active form of IRF3. In addition, NSP7 also suppressed TRIF- and STING-induced IFN responses. Mechanistically, NSP7 associated with RIG-I and MDA5 prevented the formation of the RIG-I/MDA5−MAVS signalosome and interacted with TRIF and STING to inhibit TRIF-TBK1 and STING-TBK1 complex formation, thus reducing the subsequent IRF3 phosphorylation and nu clear translocation that are essential for IFN induction. In addition, ectopic expression of NSP7 impeded innate immune activation and facilitated virus replication. Taken together, SARS-CoV-2 NSP7 dampens type I and III IFN responses via disruption of the signal transduction of the RIG-I/MDA5−MAVS, TLR3-TRIF, and cGAS-STING signaling pathways, thus providing novel insights into the interactions between SARS-CoV-2 and innate antiviral immunity. This article is protected by copyright. All rights reserved. View on Web

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The risk of acute myocardial infarction among patients with laboratory-confirmed invasive pneumococcal disease: a self-controlled case series study

alexandrossfakianakis shared this article with you from Inoreader The risk of acute myocardial infarction among patients with laboratory-confirmed invasive pneumococcal disease: a self-controlled case series study via Clinical Infectious Diseases Advance Access Abstract Background Major cardiovascular events, including acute myocardial infarction (AMI), have been reported among patients with certain viral and bacterial infections. Yet, whether invasive pneumococcal disease (IPD) increases the risk of AMI remains unclear. We examined whether laboratory-confirmed IPD was associated with the risk of AMI. Methods We conducted a self-controlled case series analysis among adult Tennessee residents with evidence of a first AM I hospitalization (2003-2019). Patient follow-up started 1 year prior to the earliest AMI and continued through the date of death, 1 year after AMI or end of study (12/2019). Periods for AMI assessment included the 7 to 1 days before IPD-specimen collection (pre IPD detection), day 0 through day 7 after IPD-specimen collection (current IPD), the 8 to 28 days after IPD-specimen collection (post IPD), and a control period (all other follow-up time). We used conditional Poisson regression to calculate incidence rate ratios and 95% confidence intervals (CI) for each risk period compared to control periods using within-person comparisons. Results We studied 324 patients hospitalized for AMI with a laboratory-confirmed IPD within 1 year before or after the AMI hospitalization. The incidence of AMI was significantly higher during the pre-IPD detection period (IRR:10.29; CI:6.33-16.73) and current IPD (IRR: 92.95; CI:72.17-119.71) periods, but non-significantly elevated in the post -IPD risk period (IRR: 1.83; CI:0.86-3.91) compared to control periods. An elevated AMI incidence was also observed in the post-IPD control period (29 to 364 days after IPD) [IRR: 2.95; CI:2.01-4.32]. Conclusions Hospitalizations with AMI were strongly associated with laboratory-confirmed IPD. View on Web

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Analysis of Unmet Information Needs Among Patients With Thyroid Cancer

alexandrossfakianakis shared this article with you from Inoreader Analysis of Unmet Information Needs Among Patients With Thyroid Cancer via JAMA Otolaryngology–Head & Neck Surgery Current Issue This survey study uses mixed-methods analysis to assess p retreatment counseling experiences of survivors of thyroid cancer and to identify their unmet information needs. View on Web

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Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers

alexandrossfakianakis shared this article with you from Inoreader Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers via JAMA Otolaryngology–Head & Neck Surgery Current Issue This prospective observational study examines if circulat ing tumor human papillomavirus DNA can be used as an accurate measure of disease status at the time of diagnosis, throughout treatment, and during monitoring in human papillomavirus-associated sinonasal and nasopharyngeal squamous cell carcinomas. View on Web

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Patterns of Infectious Disease Associated with Injection Drug Use

alexandrossfakianakis shared this article with you from Inoreader Patterns of Infectious Disease Associated with Injection Drug Use in Massachusetts via Clinical Infectious Diseases Advance Access Abstract Background Since 2014, multiple outbreaks of HIV among people who inject drugs (PWID) have occurred across the United States along with hepatitis C (HCV), skin and soft tissue infections (SSTI) and infective endocarditis (IE), creating a converging public health crisis. Methods We analyzed the temporal patterns of infectious disease and overdose (OD) using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least one HIV case in a given month as a function of the counts/rates of OD, HCV, SSTI, IE and associated medical procedures at different lagged time periods. Results Current-month HIV is associated with increasing HCV cases; abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, one additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least one current-month HIV case in a given locale (odds ratios: 1.04, 1.04; 90% credible intervals: 1.01-1.10, 1.00-1.09). No such associations were observed for echocardiograms, IE, or OD. Conclusion Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point towards newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections. View on Web

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