Mapping glycoprotein structure reveals Flaviviridae evolutionary history

Area of Science:

• Virology
• Molecular Biology
• Evolutionary Biology

Background:

• Viral glycoproteins are crucial for enveloped virus entry and pathogenesis.
• The Flaviviridae family, including hepatitis C, dengue, and Zika viruses, has poorly understood glycoproteins and fusion mechanisms.
• Many flaviviruses lack identified glycoproteins, hindering comprehension of their biology.

Purpose of the Study:

• To comprehensively survey glycoproteins across the entire Flaviviridae family.
• To characterize the evolutionary history and diversity of flavivirus glycoproteins.
• To elucidate the molecular mechanisms of membrane fusion in Flaviviridae.

Main Methods:

• Phylogenetic analyses were employed to study glycoprotein distribution.
• Protein structure prediction was utilized to analyze glycoprotein structures.
• Glycoprotein distribution was mapped onto the viral phylogeny.

Main Results:

• Most flaviviruses utilize class II fusion systems, homologous to the Orthoflavivirus E glycoprotein.
• Hepaciviruses, pegiviruses, and pestiviruses possess distinct E1E2 glycoproteins, suggesting a novel fusion mechanism.
• These distinct glycoproteins are linked to vertebrate host infections.
• Evolutionary analysis revealed gene capture from bacteria and potential inter-genus recombination.

Conclusions:

• The study refines our understanding of viral fusion mechanisms within the Flaviviridae.
• It highlights the complex evolutionary trajectory of flavivirus glycoproteins.
• Insights into glycoprotein diversity and evolution shed light on the ecology of these viruses.