Carp virus provides significant insights into immunology

In an article published in the journal Nucleic Acids Research, the team led by Prof. Alain Vanderplasschen, a virologist and immunologist at the University of Liège, describes ten years of research on how a carp virus uses a protein domain called Zalpha (Zα) to inhibit the host cell’s defense mechanisms.

This discovery has profound ramifications for how researchers understand how crucial immune system proteins with the Zα domain function.

The team of Prof. Alain Vanderplasschen, a virologist and immunologist at the FARAH (Faculty of Veterinary Medicine) of the University of Liège, can only agree that one of the exciting parts of scientific study is the serendipity that goes along with it.

The findings of 10 years of work on an original protein of a carp virus have just been published in the esteemed journal Nucleic Acids Research.

This scientific project began more than ten years ago when researchers in Lisbon discovered that a carp virus—the Cyprinid herpesvirus 3 or CyHV-3—had stolen a cellular gene coding for a protein domain called Zα during the course of evolution. It is s a virus that we know very well here at the University of Liège because we have been studying it for many years.”

Alain Vanderplasschen, Virologist and Immunologist, Faculty of Veterinary Medicine, University of Liège

The Zα domain enables proteins to recognize double-stranded DNA or RNA in an uncommon configuration that differs from the one Watson and Crick first reported in 1953.

In fact, when the double helix displays a left-handed conformation rather than a right-handed conformation, the Zα domain particularly recognizes nucleic acids. Important immune system proteins in many animals, including humans, include this Zα domain.

Prof. Vanderplasschen added, “These proteins are involved in important and diverse pathological processes such as cancers, genetic diseases and autoimmune diseases. By studying the functions of the Zα domain of the carp virus, we discovered that it possesses properties that were previously unknown for the Zα domains of cellular proteins.”

Interestingly, the researchers discovered that some cellular proteins have the new characteristics revealed for the Zα of the carp virus by genetically modifying the Zα domain of the virus into the Zα domains of cellular proteins from different animal species, including humans.

This study, which was done by ULiège researchers and was recently published, increases the functional diversity of Zα domains and inspires new theories about the mechanisms by which proteins with Zα domain function. It is a discovery that sheds fresh light on how proteins with Zα domains, which are involved in major diseases, function.