Global Phylogenetic Analysis of the CDV Hemagglutinin Gene Reveals Positive Selection on Key Receptor-Binding Sites


OĞUZOĞLU T. Ç., Koç B. T.

Viruses, cilt.17, sa.9, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 9
  • Basım Tarihi: 2025
  • Doi Numarası: 10.3390/v17091149
  • Dergi Adı: Viruses
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Anahtar Kelimeler: hemagglutinin, lineage, Nectin-4, phylogeny, SLAM
  • Ankara Üniversitesi Adresli: Evet

Özet

Canine distemper virus (CDV) is a multi-host morbillivirus whose evolution and host-switching capacity are largely determined by its hemagglutinin (H) gene. To reconsider the molecular evolution of this critical gene, we performed comprehensive phylogenetic, selection, and structural analyses on a curated dataset of 68 representative global H gene sequences. Our phylogenetic reconstruction confirmed the segregation of sequences into distinct, geographically associated lineages. To provide stronger evidence for viral adaptation, we performed a site-specific selection analysis, which identified 15 amino acid sites in the H protein undergoing significant episodic positive selection. Crucially, the majority of the known SLAM and Nectin-4 receptor-binding residues were found to be among these positively selected sites. We further contextualized these findings by mapping the sites onto a 3D homology model of the H protein, which confirmed their location on the exposed surfaces of the receptor-binding domain. This compilation provides quantitative evidence that the key functional regions of the H protein are direct targets for adaptive evolution, which has significant implications for understanding host tropism and the ongoing challenge of vaccine mismatch.