Cytomegalovirus uses a new stealth strategy to disrupt immune surveillance

A study published by the University of Barcelona researchers on April 4th in the Journal of Pathogens in the Public Science Library showed that owl monkey cytomegalovirus escapes the detection and destruction of host immune cells by producing a decoy molecule, A43.

The immune system has the function of recognizing, killing and promptly eliminating mutant cells in the body to prevent tumorigenesis, which is called immune surveillance. Immune surveillance is one of the most basic functions of the immune system. An excessively low immune surveillance function could form a tumor. This finding provides a new example of an immune evasion strategy for virus development.

Throughout the evolutionary process, cytomegaloviruses (CMVs) suppress the immune response by utilizing derived proteins produced by the host gene and use the host replication machinery to reproduce themselves in the host. Some CMVs encode a homolog of CD48, a molecule found on the surface of most white blood cells in the body.

CD48 is known to bind to the 2B4 receptor on certain immune cells, such as natural killer cells, which play a key role in the rapid identification and control of viral infections. However, the nature and biological relevance of viral CD48 homologs have been unknown.

In this new study, the research team first studied the immunomodulatory potential of A43, one of these viral molecules. A43 is a CD48 homolog encoded by Owl CMV.

The results uncovered that A43 strongly binds to 2B4 and blocks its interaction with CD48. The researchers also suggested that A43 acts as a CD48 decoy receptor by binding and masking 2B4, thereby impeding effective immune control of cytotoxic lymphocytes during viral infection. Cytotoxic lymphocytes (CTL), a sub-part of leukocytes, are a specific T cell that secretes various cytokines to participate in immune function. It has a killing effect on certain antigens, tumor cells, and other antigenic substances, and natural killer cells constitute an important line of defense against anti-virus and anti-tumor immunity.

In addition, the findings reveal how this viral protein interferes with the function of human natural killer cells. Natural killer cells (NK) are important immune cells of the body, not only related to anti-tumor, anti-viral infection and immune regulation, but also participate in hypersensitivity and autoimmune diseases in some cases, can identify target cells, kill medium.

Taken together, these results not only highlight the importance of 2B4-mediated immune responses in controlling CMV infection but also reveal a new viral offset mechanism for CD48 as subversive immune surveillance. This study emphasized the potential to develop new therapeutic tools using the inhibitory molecule A43 to manipulate abnormal immune responses, such as those associated with autoimmune diseases.
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