Related Experiment Video

Updated: Mar 13, 2026

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
07:53

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

33.9K

Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality

Dalit Talmi-Frank1, Zeev Altboum2, Inna Solomonov3

  • 1Department of Biological Regulation, Weizmann Institute, 7610001 Rehovot, Israel; Department of Immunology, Weizmann Institute, 7610001 Rehovot, Israel.

Cell Host & Microbe
|October 14, 2016
PubMed

Insights

Targeting extracellular matrix (ECM) breakdown with MT1-MMP inhibitors improved lung tissue resilience during influenza infection. Combination therapy with Oseltamivir synergistically enhanced recovery in mice.

Area of Science:

  • Immunology
  • Virology
  • Biochemistry

Background:

  • Host survival depends on balancing immune response with tissue integrity.
  • Extracellular matrix (ECM) proteolysis plays a key role in this balance during infection.

Purpose of the Study:

  • To investigate the role of ECM proteolysis in lung tissue during influenza infection.
  • To identify therapeutic targets for improving host resilience and treatment outcomes.

Main Methods:

  • Combined genomic and proteomic approaches were used.
  • Investigated the role of membrane-tethered matrix metalloprotease MT1-MMP.
  • Evaluated selective MT1-MMP inhibition and Oseltamivir treatment in influenza models, including coinfection with Streptococcus pneumoniae.

Main Results:

  • MT1-MMP was identified as a key collagenase remodeling the lung ECM during influenza.
  • Selective MT1-MMP inhibition protected lung tissue from structural and compositional damage without significantly altering immune response or cytokine levels.
  • Oseltamivir did not prevent ECM damage and was less effective than MT1-MMP inhibition in coinfection models.
  • Combination therapy of Oseltamivir with MT1-MMP inhibition demonstrated synergistic effects, leading to complete recovery in infected mice.

Conclusions:

  • Tissue resilience is crucial for surviving infections.
  • MT1-MMP is a potential therapeutic target for mitigating influenza-induced lung damage.
  • Host-directed therapies targeting ECM remodeling, especially in combination with antivirals, show promise for treating respiratory infections.
Keywords:
ECM remodelingInfluenza virusMT1-MMPhost-pathogen gene regulationimmune genomicsmatrix metalloproteinase inhibitorsviral-bacterial coinfection

More Related Videos

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection08:16

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection

Published on: July 21, 2022

1.9K
Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein09:39

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein

Published on: April 21, 2015

18.4K

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
3.6K
The Extracellular Matrix01:42

The Extracellular Matrix

Overview
90.7K
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
13.0K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.8K
Extracellular Matrix01:26

Extracellular Matrix

Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. This extracellular matrix (ECM) is composed of fibrous proteins like collagen, elastin, and fibronectin in a ground substance consisting of interstitial fluid, cell adhesion proteins, and proteoglycans. The proteoglycans form a gel-like material in the spaces between cells and provide hydration, buffering, binding, and force...
6.3K
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
3.7K