Myotis bat STING attenuates aging-related inflammation in female mice

Bats,notable as the only flying mammals,serve as natural reservoir hosts for various highly pathogenic viruses in humans(e.g.,SARS-CoV and Ebola virus).Furthermore,bats exhibit an unparalleled longevity among mammals relative to their size,particularly the Myotis bats,which can live up to 40 years.However,the mechanisms underlying these distinctive traits remain incompletely understood.In our prior research,we demonstrated that bats exhibit dampened STING-interferon activation,potentially conferring upon them the capacity to mitigate virus-or aging-induced inflammation.To substantiate this hypothesis,we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING(MdSTING)into the mouse genome.We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process.Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice,as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines,immunopathology,and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo.These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner.Although the underlying mechanism awaits further study,this research has critical implications for bat longevity research,potentially contributing to our comprehension of healthy aging in humans.

ACE2-independent infection of T lymphocytes by SARS-CoV-2

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19.However,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from patients.Here,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive PBCs.We next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in vitro.Upon infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T cells.Furthermore,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments.Next,we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis.In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways.Finally,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known receptors.Collectively,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.