Related Experiment Video

Updated: Jul 5, 2026

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif

Jason W Upton1, William J Kaiser, Edward S Mocarski

  • 1Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

The Journal of Biological Chemistry
|April 30, 2008
PubMed

Insights

Murine cytomegalovirus M45 protein inhibits receptor-interacting protein (RIP) signaling, preventing premature endothelial cell death. This viral strategy enhances virus replication and modulates host innate immune responses.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Herpesviruses, including cytomegaloviruses, possess proteins that interfere with host innate immune responses to promote viral survival.
  • The murine cytomegalovirus (MCMV) M45 protein is known to interact with key host signaling molecules.

Purpose of the Study:

  • To investigate the role of the MCMV M45 protein in modulating host cell death pathways.
  • To elucidate the molecular mechanisms by which M45 interacts with receptor-interacting proteins (RIPs) and its impact on viral replication and host defense.

Main Methods:

  • Analysis of M45 protein interactions with RIP1 and RIP3 using co-immunoprecipitation assays.
  • Assessment of cell death suppression by M45 in endothelial cells during MCMV infection.
  • Investigation of M45's role in modulating Toll-like receptor (TLR) signaling pathways.

Main Results:

  • The M45 protein interacts with RIP1 and RIP3 through a RIP homotypic interaction motif.
  • M45-mediated suppression of cell death is dependent on its interaction with RIP1.
  • This interaction is crucial for preventing premature endothelial cell death, thereby facilitating viral replication in a cell type-dependent manner.
  • M45 modulates RIP1-mediated signaling, including Toll-like receptor 3 activation and other cell death mediators.

Conclusions:

  • The MCMV M45 protein acts as a viral inhibitor of RIP activation, providing a replication advantage to the virus.
  • M45's interaction with RIP1 is critical for both cell death suppression and determining viral cell tropism.
  • This viral protein plays a significant role in manipulating host innate immunity and cell death pathways during cytomegalovirus infection.

More Related Videos

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Related Concept Videos

Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...