Thursday, 08 April 2021 16:49

The structure of an adenovirus that infects lizards illustrates the role of viruses as major players in life evolution

Differences between the capsids of a human (left) and a lizard (right) adenovirus where proteins IX and LH3 are depicted in gold. Differences between the capsids of a human (left) and a lizard (right) adenovirus where proteins IX and LH3 are depicted in gold. Carmen San Martín, CNB-CSIC
  • Researchers from the CNB-CSIC, the UAM and the Institute Pasteur use high-resolution cryoelectron microscopy to solve the structure of an adenovirus that infects lizards
  • Combining structural data and sequence analysis they show how these viruses acquired in the past a gene from a bacteria and used it to produce a protein that stabilises their capsid
  • Throughout evolution, adenoviruses began to infect mammals and the function of the gene changed once again, becoming an oncoprotein capable of altering the division cycle of the infected cells

Scientists from the Spanish National Research Council (CSIC), the Autónoma University in Madrid (UAM) and the Pasteur Institute in France have solved for the first time the high resolution structure of an atadenovirus, a type of adenovirus that infects lizards. Until now, the only adenovirus structures known belonged to adenoviruses that infect mammals, although there are more than 200 adenoviruses that can infect other species and would have a potential therapeutical use as alternative vectors in the development of vaccines or gene therapy treatments.

This new high-resolution viral structure, published in Science Advances by Carmen San Martín group at the National Centre for Biotechnology (CNB-CSIC), shows an important difference in the surface of the atadenovirus capsid: the presence of a protein called LH3 that does not exist in the human adenovirus, but whose capsid anchoring domain is structurally identical to that of human adenovirus protein IX, despite the fact that both proteins have a completely different sequence. For San Martín, "the fact that both viruses evolve to preserve a specific structure reveals its importance for the formation and global maintenance of the capsid, and therefore the survival of the virus." "In addition, there is another part of LH3 that resembles the E1B-55K protein of human adenoviruses, which is not part of the capsid, but rather interferes with the cell division cycle."

In collaboration with the Pasteur Institute in France, the researchers analysed the adenovirus genome evolution and found that these structural similarities are due to an ancestral duplication of the LH3 gene and a subsequent differential evolution. "These results indicate that a common ancestor of reptilian and mammalian adenoviruses acquired the LH3 gene from bacteria or bacteriophages, probably when they met in the same environment (for example, the intestine of an animal)" indicates Gabriela Condezo, researcher from the CNB-CSIC that participates in the study. “Later, the gene was duplicated, and each of the two copies evolved independently, until they reached what we see today in human adenoviruses. One of the copies changed drastically and kept only the small part that allows the protein to anchor to the capsid, becoming protein IX. The other copy lost the anchoring part and ceased to be part of the viral particle, becoming nothing less than an oncoprotein ”For Roberto Marabini, researcher at the UAM, “these data allow us to see a small part of the evolutionary history of adenoviruses, which probably changed as the host organisms also evolved. Furthermore, they show us how viruses reuse and transform genes from other organisms, generating new functions for proteins during evolution”. Knowledge on the structure and function of non-human adenoviruses is relevant in the global health context, since they are pathogens for animals with economic (birds, ruminants) or ecological (reptiles, amphibians) importance. In addition, they have potential as therapeutic tools alternative to human adenoviruses , for which a large part of the general population already has an immune response, making them less effective as drugs. This is why, for example, some of the SARS-CoV-2 vaccines  use a chimpanzee adenovirus instead of a human one to generate an efficient immune response against coronavirus proteins.

More information:

Near Atomic Structure of an Atadenovirus Reveals a Conserved Capsid-Binding Motif and Intergenera Variations in Cementing Proteins. Marabini R, Condezo GN, Krupovi M., Menéndez-Conejero R, Gómez-Blanco J, and San Martín C. Sci Adv 2021, 7 (14) doi: 10.1126/sciadv.abe6008.

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