Genetic substructure and host-specific natural selection trend across vaccine-candidate ORF-2 capsid protein of hepatitis-E virus.

Autor: Khan N; Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan., Kakakhel S; Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan., Malik A; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Nigar K; Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan., Akhtar S; Department of Biochemistry, A.T. Still University of Health Sciences, Kirksville, Missouri, USA., Khan AA; Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Khan A; Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan.
Jazyk: angličtina
Zdroj: Journal of viral hepatitis [J Viral Hepat] 2024 Sep; Vol. 31 (9), pp. 524-534. Date of Electronic Publication: 2024 May 28.
DOI: 10.1111/jvh.13959
Abstrakt: Hepatitis E virus is a primary cause of acute hepatitis worldwide. The present study attempts to assess the genetic variability and evolutionary divergence among HEV genotypes. A vaccine promising capsid-protein coding ORF-2 gene sequences of HEV was evaluated using phylogenetics, model-based population genetic methods and principal component analysis. The analyses unveiled nine distinct clusters as subpopulations for six HEV genotypes. HEV-3 genotype samples stratified into four different subgroups, while HEV-4 stratified into three additional subclusters. Rabbit-infectious HEV-3ra samples constitute a distinct cluster. Pairwise analysis identified marked genetic distinction of HEV-4c and HEV-4i subgenotypes compared to other genotypes. Numerous admixed, inter and intragenotype recombinant strains were detected. The MEME method identified several ORF-2 codon sites under positive selection. Some selection signatures lead to amino acid substitutions within ORF-2, resulting in altered physicochemical features. Moreover, a pattern of host-specific adaptive signatures was identified among HEV genotypes. The analyses conclusively depict that recombination and episodic positive selection events have shaped the observed genetic diversity among different HEV genotypes. The significant genetic diversity and stratification of HEV-3 and HEV-4 genotypes into subgroups, as identified in the current study, are noteworthy and may have implications for the efficacy of anti-HEV vaccines.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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