[Chuan Ku] Membrane fusion proteins shed light on the origin and evolution of giant viruses

Fusion between virus and host membranes is critical for viruses to release genetic materials and to initiate infection. Whereas most viruses use a single protein for membrane fusion, a multi-protein entry-fusion complex (EFC) is necessary for cell entry by poxviruses, which cause important diseases such as smallpox and monkeypox. Poxviruses belong to the phylum Nucleocytoviricota, which includes other “giant viruses” with extraordinary genome and particle size comparable to that of small bacteria and infects diverse eukaryotes encompassing animals, amoebozoans, algae, and various microeukaryotes. To unravel the origin of the poxviral EFC, the labs of Chuan Ku (Institute of Plant and Microbial Biology) and Wen Chang (Institute of Molecular Biology) conducted a comprehensive genomic survey of giant viruses and found that the two major EFC protein families are widely distributed across giant viruses. Each of these two protein families is structurally conserved, traces its origin to the root of Nucleocytoviricota, was passed down to the major descendant lineages of Nucleocytoviricota, and is retained in most giant viruses that are known to infect animals and amoebozoans. Overall the findings indicate that the EFC proteins represent a potentially conserved mechanism for cell entry in diverse giant viruses. It further suggests that the EFC proteins may have facilitated the infection of an animal/amoebozoan-like host by the last Nucleocytoviricota common ancestor and that losses of EFC proteins might be associated with shifts to other eukaryotic hosts such as algae. By extending the knowledge gained from model poxvirus systems, this work provides insights into the origin, evolution, and biology of the enigmatic giant viruses.

The study has been published in the journal Microbiology Spectrum. It was funded by an Academia Sinica Career Development Award (AS-CDA-110-L01) and the National Science and Technology Council, Taiwan.

Publication: Sheng Kao, Chi-Fei Kao, Wen Chang, Chuan Ku (2023): Widespread distribution and evolution of poxviral entry-fusion complex proteins in giant viruses. Microbiology Spectrum 11: e04944-22.