A quadruple recombination event discovered in hepatitis E virus

Even after three decades of antiretroviral therapy for HIV-1, therapy failure is a continual challenge. This is especially so, if the viral variant is a recombinant of subtypes. Thus, improved diagnosis of recombined subtypes can help with the selection of therapy. We are using a new implementation of the previously published computational method recco to detect de novo recombination of known subtypes, independent of and in addition to known circulating recombinant forms (CRFs). We detect an optimal path in a multiple alignment of viral reference sequences based on mutation calls and probable breakpoints for recombination. A tuning parameter is used to favor either mutation calls or breakpoints. Besides novel recombinants, our tool g2p-recco integrated in the geno2pheno web-service https://geno2pheno.org can successfully detect known recombinant events given only the full consensus references (without CRFs) of the involved subtypes with breakpoints. In addition, the tool can be applied to other viruses, i.e hepatitis E virus (HEV). In this fashion, we could also detect several previously unknown recombinations in HEV.

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

Khan,

Kakakhel,

Malik

et al. 2024

Journal of Viral Hepatitis

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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.

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A quadruple recombination event discovered in hepatitis E virus

Cited by 3 publications

References 16 publications

Hepatitis E virus species barriers: seeking viral and host determinants

Hepatitis E virus species barriers: seeking viral and host determinants

Geno2pheno: recombination detection for HIV-1 and HEV subtypes

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

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