Function and regulation of cGAS-STING signaling in infectious diseases.

The efficacious detection of pathogens and prompt induction of innate immune signaling serve as a crucial component of immune defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have emerged as key mediators of type I interferon (IFN) and nuclear factor-κB (NF-κB) responses in health and infection diseases. Moreover, both cGAS-STING pathway and pathogens have developed delicate strategies to resist each other for their survival. The mechanistic and functional comprehension of the interplay between cGAS-STING pathway and pathogens is opening the way for the development and application of pharmacological agonists and antagonists in the treatment of infectious diseases. Here, we briefly review the current knowledge of DNA sensing through the cGAS-STING pathway, and emphatically highlight the potent undertaking of cGAS-STING signaling pathway in the host against infectious pathogenic organisms.

Development of an indirect ELISA to detect PEDV specific IgA antibody based on a PEDV epidemic strain.

BACKGROUND: Porcine epidemic diarrhea (PED), a swine epidemic disease caused by porcine epidemic diarrhea virus (PEDV), is characterized by severe watery diarrhea, vomiting, dehydration and high mortality in piglets, and has caused serious economic losses to the global porcine industry. The level of PEDV IgA antibody is a key marker to assess the extent of passive immunity of the resistance against PEDV infection. However, current commercial structure proteins-based kits for detection of PEDV antibody are not affordable, and those kits require complicated antigen preparation procedures, which cannot meet the scope of economic benefits of many large-scale pig companies in China. Therefore, there is an urgent need to develop an accurate, simple, and economical method for IgA detection in clinical samples. In this study, an indirect ELISA (i-ELISA) method was developed based on a purified PEDV epidemic strain (NH-TA2020). RESULTS: The results show that optimal working dilution ratios of PEDV antigen and HRP anti-swine IgA are at 1: 1000 and 1:15000 respectively. The sensitivity of this method is high with the maximum dilution of samples up to 1:160, and coefficients of variation (CV) of both the intra assays and inter assays were no more than 15%. In addition, the relative sensitivities of the i-ELISA were above 90% compared with values from commercial kits in both serum and oral fluid samples. CONCLUSIONS: Our results suggested that the i-ELISA developed in this study was an accurate, simple, and economical method for PEDV-IgA detection in clinical samples.

Coronavirus interactions with the cellular autophagy machinery.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting.