« Z » for Zalpha

Since the early 2000s, carp farms (koi and common carp) have been decimated by a virus, the Cyprinid herpesvirus 3, with a considerable economic impact. A few years ago, Alain Vanderplasschen's laboratory succeeded in cloning the virus genome and developing a vaccine.  In 2020, this technology was the subject of a marketing agreement with a Chinese company, as the Chinese market represents 80% of the world's carp production.

In a new study that appeared on the cover of Nucleic Acids Research, Alain Vanderplasschen's laboratory highlighted the role of the Zalpha domain, a particular protein domain of the virus, in viral replication. Its expression ensures virulence in carp and, conversely, the deletion of part of this Zalpha domain is deleterious for the virus.

In particular, the Zalpha domain binds to double-stranded DNA or RNA in a specific conformation known as a "left-handed double helix" (as opposed to the known right-handed double helix conformation of DNA as described by Watson and Crick). This binding will affect the concentration gradient of certain proteins in the cytoplasm of infected cells, acting as a protective shield that prevents the infected cell from detecting the viral infection.

The team also showed that these properties of the Zalpha domain discovered in Cyprinid herpesvirus 3 were also present in the Zalpha domains of certain human proteins. Zalpha domains are found in important proteins of the immune system and are involved in pathological processes such as cancers, genetic diseases and autoimmune diseases. This study provides new insights into the roles of Zalpha domains in the functioning of the immune system and may lead to new strategies for pharmacological inhibition of these Zalpha domains.

Reference : Mamadou Amadou Diallo et al (2023), Nucleic Acids Research, Vol 51, Issue2

Illustration : With the permission of Nucleic Acids Research