Abstract:The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation. cGAS recognizes chromatin DNA… Show more
“…Like other coronaviruses, SARS-CoV-2 RNA is detected by endosomal Toll-like receptor (TLR)-2, TLR3 and TLR7 ( 12 ) or cytosolic retinoic acid-induced gene 1 (RIG-1) and melanoma differentiation-associated gene 5 (MDA5) ( 13 ). It has been reported that SARS-CoV-2 infection can also be detected through the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway ( 14 ). Viral detection triggers the activation of various transcription factors resulting in the secretion of pro-inflammatory chemokines and cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 and IL-6, amongst others, by monocytes, macrophages, neutrophils, and dendritic cells (DCs) that home to the site of infection ( 12 , 13 , 15 ).…”
Section: Natural Vs Vaccine-induced Immunity To Sars-cov-2mentioning
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta coronavirus that emerged at the end of 2019 in the Hubei province of China. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as a strategy to protect the vulnerable, and can be established through immunity from past infection or vaccination. Whether SARS-CoV-2 infection results in the development of a reservoir of resilient memory cells is under investigation. Vaccines have been developed at an unprecedented rate and 7 408 870 760 vaccine doses have been administered worldwide. Recently emerged SARS-CoV-2 variants are more transmissible with a reduced sensitivity to immune mechanisms. This is due to the presence of amino acid substitutions in the spike protein, which confer a selective advantage. The emergence of variants therefore poses a risk for vaccine effectiveness and long-term immunity, and it is crucial therefore to determine the effectiveness of vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity. We further discuss how variants emerge and the currently circulating variants of concern (VOC), with particular focus on implications for vaccine effectiveness. Finally, we describe new antibody treatments and future vaccine approaches that will be important as we navigate through the COVID-19 pandemic.
“…Like other coronaviruses, SARS-CoV-2 RNA is detected by endosomal Toll-like receptor (TLR)-2, TLR3 and TLR7 ( 12 ) or cytosolic retinoic acid-induced gene 1 (RIG-1) and melanoma differentiation-associated gene 5 (MDA5) ( 13 ). It has been reported that SARS-CoV-2 infection can also be detected through the cytosolic DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway ( 14 ). Viral detection triggers the activation of various transcription factors resulting in the secretion of pro-inflammatory chemokines and cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1 and IL-6, amongst others, by monocytes, macrophages, neutrophils, and dendritic cells (DCs) that home to the site of infection ( 12 , 13 , 15 ).…”
Section: Natural Vs Vaccine-induced Immunity To Sars-cov-2mentioning
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new beta coronavirus that emerged at the end of 2019 in the Hubei province of China. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19) and was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. Herd or community immunity has been proposed as a strategy to protect the vulnerable, and can be established through immunity from past infection or vaccination. Whether SARS-CoV-2 infection results in the development of a reservoir of resilient memory cells is under investigation. Vaccines have been developed at an unprecedented rate and 7 408 870 760 vaccine doses have been administered worldwide. Recently emerged SARS-CoV-2 variants are more transmissible with a reduced sensitivity to immune mechanisms. This is due to the presence of amino acid substitutions in the spike protein, which confer a selective advantage. The emergence of variants therefore poses a risk for vaccine effectiveness and long-term immunity, and it is crucial therefore to determine the effectiveness of vaccines against currently circulating variants. Here we review both SARS-CoV-2-induced host immune activation and vaccine-induced immune responses, highlighting the responses of immune memory cells that are key indicators of host immunity. We further discuss how variants emerge and the currently circulating variants of concern (VOC), with particular focus on implications for vaccine effectiveness. Finally, we describe new antibody treatments and future vaccine approaches that will be important as we navigate through the COVID-19 pandemic.
“…Alternatively, Ren et al found that SARS-CoV-2 may activate IFN response unexpectedly via the cGAS-STING signaling pathway, which was induced by the cytoplasmic micronuclei produced in the multinucleate syncytia between cells expressing spike and ACE2 [ 95 ]. And the results were further confirmed independently by Zhou et al, who demonstrated that cell-cell fusion was sufficient to induce cytoplasmic chromatin, and the cytoplasmic chromatin-cGAS-STING pathway, but not the MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion [ 96 ]. Interestingly, several SARS-CoV-2 proteins (3CLpro, ORF3a, and ORF9) were also able to target STING to regulate the IFN response [ 97 ], likely indicating a complex feedback interaction between SARS-CoV-2 and the innate immunity, and therefore a well-balanced immune interference targeting IFN response is required for COVID-19 therapy.…”
Section: Targeting the Type I Ifn Production By Sars-cov-2mentioning
The coronavirus disease 2019 (COVID-19) has been a global pandemic for more than 2 years and it still impacts our daily lifestyle and quality in unprecedented ways. A better understanding of immunity and its regulation in response to SARS-CoV-2 infection is urgently needed. Based on the current literature, we review here the various virus mutations and the evolving disease manifestations along with the alterations of immune responses with specific focuses on the innate immune response, neutrophil extracellular traps, humoral immunity, and cellular immunity. Different types of vaccines were compared and analyzed based on their unique properties to elicit specific immunity. Various therapeutic strategies such as antibody, anti-viral medications and inflammation control were discussed. We predict that with the available and continuously emerging new technologies, more powerful vaccines and administration schedules, more effective medications and better public health measures, the COVID-19 pandemic will be under control in the near future.
“…Some studies stressed that the STING agonists block the SARS-CoV-2 infection via triggering the type I interferons (IFNs) response, 2 , 3 while others revealed that SARS-CoV-2 induces the chromatin DNA traveling to cytosol by promoting the cell-to-cell fusion, resulting in the activation of cGAS-STING signaling. 4 This paper provides a new perspective regarding the role of cyclic GMP-AMP synthase (cGAS)-STING pathway in pulmonary inflammation during SARS-CoV-2 infection. Fig.…”
mentioning
confidence: 99%
“… 2 – 5 DiABZI, a STING agonist, effectively blocks SARS-CoV-2 infection by stimulating type I IFN responses. 2 , 3 While Rui et al 5 revealed that SARS-CoV-2 suppressed the cGAS-STING pathway via ORF3a and 3CL, Zhou et al 4 showed that SARS-CoV-2 promotes cell-to-cell fusion via spike protein, leading to chromatin DNA shuttling from the nucleus and triggering the cGAS-STING pathway eventually. It remains to be investigated whether SARS-CoV-2 activates the cGAS-STING pathway via other mechanisms at the alveolus-capillary interface.…”
mentioning
confidence: 99%
“…Domizio et al 1 , 4 put great efforts into studying the skin lesions during SARS-CoV-2 infection. COVID-19 profiles exhibited aberrant inflammatory response signatures resembling cutaneous lupus erythematosus (CLE) samples.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
