Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19

Liu, Yuying; Lv, Jiadi; Liu, Jiangning; Li, Man; Xie, Jing; Lv, Qi; Deng, Wei; Zhou, Nannan; Zhou, Yabo; Song, Jiangping; Wang, Peng; Qin, Chuan; Tong, Wei‐Min; Huang, Bo

doi:10.1038/s41422-020-00435-z

Cited by 109 publications

(102 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S6c, d ). Our previous study has shown that SARS-CoV-2 infection causes the production of mucus in the alveoli, thus aggravating the pathological damage 34 . Here, we found that the depletion of AMs relieved this mucous production (Fig.…”

Section: Resultsmentioning

confidence: 99%

Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

et al. 2021

Self Cite

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades the alveoli, where abundant alveolar macrophages (AMs) reside. How AMs respond to SARS-CoV-2 invasion remains elusive. Here, we show that classically activated M1 AMs facilitate viral spread; however, alternatively activated M2 AMs limit the spread. M1 AMs utilize cellular softness to efficiently take up SARS-CoV-2. Subsequently, the invaded viruses take over the endo-lysosomal system to escape. M1 AMs have a lower endosomal pH, favoring membrane fusion and allowing the entry of viral RNA from the endosomes into the cytoplasm, where the virus achieves replication and is packaged to be released. In contrast, M2 AMs have a higher endosomal pH but a lower lysosomal pH, thus delivering the virus to lysosomes for degradation. In hACE2 transgenic mouse model, M1 AMs are found to facilitate SARS-CoV-2 infection of the lungs. These findings provide insights into the complex roles of AMs during SARS-CoV-2 infection, along with potential therapeutic targets.

show abstract

Section: Resultsmentioning

confidence: 99%

Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…One of the many pathways regulated by HSP90 chaperones includes the aryl hydrocarbon receptor (AhR) signalling pathway (Pongratz et al, 1992). During SARS-CoV-2 infection, AhR promotes interferon-induced mucus production in a rodent model (Liu et al, 2020). This build-up of alveolar mucus is thought to underly the obstructed blood-gas exchange seen in SARS-CoV-2 patients, thus leading to hypoxia and reduced lung capacity.…”

Section: Discussionmentioning

confidence: 99%

SARS‐CoV‐2 infection remodels the host protein thermal stability landscape

Selkrig

Stanifer

Mateus

et al. 2021

Molecular Systems Biology

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS-CoV-2 hijacks host cellular machineries on a system-wide scale so that potential host-directed therapies can be developed. In situ proteome-wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS-CoV-2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS-CoV-2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS-CoV-2 infection.

show abstract

“…Because AHR activity can be regulated by small molecules, AHR is an attractive target for therapeutic immunomodulation in the context of virus infection. Indeed, in pre-clinical models, AHR antagonists were shown to ameliorate ZIKV congenital syndrome in mice ( 106 ), increased survival in IAV infected mice ( 135 ) and reduce lung pathology induced by SARS-CoV-2 in hACE2-transgenic mice ( 136 ). However, clinical studies evaluating the safety and efficacy of targeting AHR for the treatment of viral infections are lacking.…”

Section: Therapeutic Modulation Of Ahr Activity In Clinical Practicementioning

confidence: 99%

The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

2021

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which interacts with a wide range of organic molecules of endogenous and exogenous origin, including environmental pollutants, tryptophan metabolites, and microbial metabolites. The activation of AHR by these agonists drives its translocation into the nucleus where it controls the expression of a large number of target genes that include the AHR repressor (AHRR), detoxifying monooxygenases (CYP1A1 and CYP1B1), and cytokines. Recent advances reveal that AHR signaling modulates aspects of the intrinsic, innate and adaptive immune response to diverse microorganisms. This review will focus on the increasing evidence supporting a role for AHR as a modulator of the host response to viral infection.

show abstract

Mucus production stimulated by IFN-AhR signaling triggers hypoxia of COVID-19

Cited by 109 publications

References 47 publications

Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages

SARS‐CoV‐2 infection remodels the host protein thermal stability landscape

The Aryl Hydrocarbon Receptor as a Modulator of Anti-viral Immunity

Contact Info

Product

Resources

About