Research reveals how carp virus uses protein domain to inhibit host cell defense mechanisms

The team of Pr Alain Vanderplasschen, virologist and immunologist at the University of Liège, published an article in the journal Nucleic acid research, reporting on ten years of research on how a carp virus uses a protein domain called Zalpha (Zα) to inhibit host cell defense mechanisms. Importantly, this discovery has implications for our understanding of the functions of important proteins containing the Zα domain of the immune system.

One of the fascinating aspects of scientific research is certainly the serendipity that accompanies it, with which the team of Pr Alain Vanderplasschen, virologist and immunologist at the FARAH (Faculty of Veterinary Medicine) of the University of Liège can only ‘to agree. His team has just published in the prestigious journal Nucleic acid research the results of ten years of research on the study of an original protein of a carp virus.

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

Pr Alain Vanderplasschen, Virologist and Immunologist, FARAH (Faculty of Veterinary Medicine), University of Liège

The Zα domain allows proteins that possess it to recognize double-stranded DNA or RNA in a rare conformation different from that described by Watson and Crick in 1953. Indeed, the Zα domain specifically recognizes nucleic acids when the double helix exhibits a left-handed helix conformation instead of a right-handed conformation. This Zα domain is found in important immune system proteins of many animals, including humans.

These proteins are involved in important and diverse pathological processes such as cancers, genetic diseases and autoimmune diseases.. By studying the functions of the domain Zα of the carp virus, we have discovered that it has hitherto unknown properties for the cellular protein domains” says Alain Vanderplasschen.

Remarkably, by genetically modifying the Zα domain of the virus in the Zα domains of cellular proteins from various animal and human species, the researchers discovered that the new properties discovered for the Zα of the carp virus were present in certain cellular proteins. This study, conducted by researchers at ULiège and published today, expands the functional diversity of Zα domains and stimulates new hypotheses regarding the mechanisms of action of proteins containing Zα domains. This is a discovery that opens up new perspectives on the mechanisms of action of Zα domain proteins involved in serious pathologies.

Source:

Journal reference:

Diallo, MA, et al. (2022) A fish herpesvirus demonstrates functional diversities among Zα domains related to phase separation induction and A to Z conversion. Nucleic acid research. doi.org/10.1093/nar/gkac761