Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

10.0K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.0K
Complement System01:27

Complement System

6.1K
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
6.1K
Sympathetic Activation01:16

Sympathetic Activation

6.0K
The sympathetic division can influence tissues and organs by releasing norepinephrine at peripheral synapses and distributing epinephrine and norepinephrine through the bloodstream. In times of crisis or stress, sympathetic activation occurs, which is regulated by sympathetic centers in the hypothalamus. As a result, sympathetic activation prepares the body for physical exertion, rapid ATP production, and heightened alertness, allowing individuals to respond effectively to challenging or...
6.0K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

7.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.2K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

5.7K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.7K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

1.2K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

IgA is necessary and sufficient to prevent norovirus infection in mice.

Science translational medicine·2026
Same author

RUNX2 promotes chromatin accessibility and WNT signaling in inflamed intestinal epithelial cells.

Mucosal immunology·2026
Same author

GPR15-guided CD8<sup>+</sup> T regulatory cells control intestinal inflammation.

Nature·2026
Same author

Exosome-like biogenesis from the Golgi releases extracellular vesicles lacking conventional tetraspanins that mediate immune evasion in cancer.

bioRxiv : the preprint server for biology·2026
Same author

Does Consuming Fresh Ultraviolet Light-Exposed Mushrooms Offset the Seasonal Decline in Serum Total 25OHD in Adults Classified as Overweight and Class I Obese? Results from a Randomized Controlled Trial.

Foods (Basel, Switzerland)·2026
Same author

Associations Between Routinely Measured Biomarkers and Pancreatic Cancer Risk in Individuals with Type 2 Diabetes Pre- and Post-Diagnosis.

Cancers·2026
Same journal

Erratum for the Research Article "Claudins interact with LILRB immune inhibitory receptors to promote myeloid immunosuppression in cancer".

Science immunology·2026
Same journal

Langerhans cell control of early-life dermal lymphatic development shapes adult immunity.

Science immunology·2026
Same journal

T<sub>reg</sub> cells promote immunotherapy-induced immune evasion by restraining CD4 T cell control of MHC-I-deficient metastatic pancreatic cancer.

Science immunology·2026
Same journal

CXCL16-mediated recruitment of γδ T cells to the brain reduces sociability in mice.

Science immunology·2026
Same journal

Bioactive enhanced adjuvant chemokine oligonucleotide nanoparticles (BEACONs) for mucosal vaccination against genital herpes.

Science immunology·2026
Same journal

Bacterial infection reshapes monocyte and macrophage ontogeny at the CNS borders.

Science immunology·2026
See all related articles

Related Experiment Video

Updated: Nov 9, 2025

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

597

SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation.

Bingyu Yan1, Tilo Freiwald2,3,4, Daniel Chauss2

  • 1Department of Biochemistry, Purdue University, West Lafayette, IN, USA.

Science Immunology
|April 8, 2021
PubMed
Summary
This summary is machine-generated.

SARS-CoV-2 infection activates the complement system in lung cells, a pathway linked to COVID-19 severity. JAK inhibitors like Ruxolitinib show potential in treating severe cases by normalizing complement and interferon pathways.

More Related Videos

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
08:41

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2

Published on: November 5, 2021

3.0K
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
05:23

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

6.3K

Related Experiment Videos

Last Updated: Nov 9, 2025

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
10:21

Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma

Published on: September 20, 2024

597
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
08:41

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2

Published on: November 5, 2021

3.0K
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
05:23

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

6.3K

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, affects multiple organs including lungs, liver, kidneys, and gut.
  • The Angiotensin Converting Enzyme 2 (ACE2) receptor is crucial for SARS-CoV-2 entry, and it's highly expressed in affected tissues.
  • The precise molecular pathways driving COVID-19 pathogenesis remain incompletely understood.

Purpose of the Study:

  • To investigate intracellular pathways induced by SARS-CoV-2 infection in lung epithelial cells.
  • To explore the role of the complement system in COVID-19 pathogenesis.
  • To identify potential therapeutic targets for severe COVID-19.

Main Methods:

  • Analysis of intracellular pathways in SARS-CoV-2 infected lung epithelial cells.
  • Assessment of complement activation markers (C3a) and inhibition using complement factor B inhibitor (CFBi).
  • Examination of complement activation signatures in bronchoalveolar lavage cells from COVID-19 patients.
  • Gene expression analysis to identify signaling pathways (Interferon-JAK/STAT, NF-κB) involved.
  • In vitro testing of Ruxolitinib (JAK1/2 inhibitor) and its combination with remdesivir.

Main Results:

  • The complement system was unexpectedly found to be highly induced intracellularly by SARS-CoV-2 in lung epithelial cells.
  • SARS-CoV-2 infection led to activated complement component C3a production, inhibitable by CFBi, indicating an intrinsic C3 convertase.
  • Complement activation patterns in patient cells correlated with COVID-19 disease severity.
  • Interferon-JAK1/2-STAT1 and NF-κB signaling pathways were identified as key drivers of SARS-CoV-2-induced gene expression.
  • Ruxolitinib normalized interferon-related genes and SARS-CoV-2-induced complement transcripts but not NF-κB genes.
  • Ruxolitinib, alone or with remdesivir, reduced C3a production in infected cells.

Conclusions:

  • SARS-CoV-2 infection induces an intracellular complement pathway in respiratory epithelial cells.
  • JAK-STAT and NF-κB signaling pathways are critical in COVID-19 pathogenesis.
  • Combination therapy with JAK inhibitors and NF-κB-targeting drugs may offer a potential clinical strategy for severe COVID-19.