Comprehensive Analysis Of Viral Genomes Evolution:Emergence,Re-Emergence,and Adaptation Of Viruses “sHEV,HDV,PHEV,CPV-2,CSFV,NDV,and ZIKV.”

The world is increasingly interconnected,and the emergence and re-emergence of rapidly evolving viruses with the risk of future outbreaks of animal and human infections seriously threaten global health.Comprehensive and timely surveillance systems based on genomics are critical for identifying the new variants and lineages that increase viral dispersal and help achieve an effective response.This dissertation aimed to identify different forces driving the sustained evolution of pathogens and to genotype,re-genotype,or update the molecular classification systems of several viruses.Herein,the work tried to fill the knowledge gaps,address research inconsistencies,and provide policymakers with valuable information for public health management and the prevention and control strategies of several infectious diseases.The investigated problems are as follows:Chapter 1 investigated a Betacoronavirus named Porcine hemagglutinating encephalomyelitis virus(PHEV)using the earliest full-length genome sequence information of virus PHEV/67N/US/1970 collected in the USA in 1970 and determined in October 2020,as a prototype reference.The genomic structure of all available complete genome sequences(1970 ～2020)analysis showed that USA 2015 strain clustered into a clade different from that of the earliest strain.Multiple deletion mutation patterns in the USA strain(2015)and the Belgium strain(2005),a hypervariability of S protein and eight potential linear B cell epitopes in the S gene were determined,indicating that PHEV in the USA underwent a significant genetic drift.Chapter 2 focused on screening the molecular characteristics of zoonotic swine Hepatitis E virus in China compared to other countries using the phylogenetic and recombination analysis of s HEV complete genomic sequences isolated during the past two decades.s HEV type 4 is found to dominate China.A comparison of genomic similarities revealed that s HEV3 and s HEV4 strains isolated in China fell into different groups.Eight potential natural recombination events were identified,four of which occurred in China and were mainly between s HEV4 strains indicating the distinct character of China viruses.Chapter 3 updated the molecular classification system of Hepatitis Delta virus(HDV),one of the most devastating forms of viral hepatitis,and explored the role of recombination in the worldwide genotypic distribution of HDV by analyzing a large set of human HDV complete genome sequences isolated between 1986～2018.Recombination mapping identified 48 recombination events,29 of which were collected in Kyrgyzstan.The outcome analysis indicates that HDV-RNA has complex replicative molecular mechanisms and suggests that the genomic character of Kyrgyzstan strains and extensive mobility within countries and across borders drive the diversity and extension of human HDV subgenotypes.The work provides critical information on HDV epidemiology,evolution,and clinical outcome.Chapter 4 studied the classical swine fever virus(CSFV).Since the adopted classification is initially based on partial genomes,this work proposed a re-genotyping based on complete genomic sequences of CSFV collected worldwide between 1977～2018.A mixed population of CSFV genotypes and sub-genotypes was identified co-circulating in China,Germany,and South Korea,and a new sub-genotype GI-2.2b was found restricted to China.Further,the highly virulent and vaccine strains were all identified as involved in natural recombination.This work exhibited that natural recombination was driving the genetic diversity of CSFV strains,suggested a cautious application of attenuated vaccines,and recommended using subunit vaccines for more effective CSFV controlChapter 5 attempted to make a step in the genotyping classification of canine parvovirus-2(CPV-2)since parvovirologists still refer to the three antigenic variants categorized based on the amino acid substitutions in the VP2 structural protein.The study proposed a genotyping classification with three evolutionary pathways separating the USA and China clusters and initiated a set of standard reference sequences for each genotype of CPV-2 complete genomes.Using Parsimony-Informative Sites,sequence substitutions were identified within NS1,NS2,and VP1.This work determined for the first time the occurrence of natural recombination among the latest CPV-2 strains(2017～2020),which is speculated to shape the adaptation and transmissibility of CPV-2 and is supposed to help CPV-2c escape the immune response.This work will contribute to potentially avoiding further research inconsistency and contribute to achieving a more reliable CPV-2 genotyping classification.Chapter 6 explored the genetic characteristics of Newcastle Disease Virus(NDV)in China using all complete genomes collected from 26 provinces between 1946～2020.This work determined two groups of NDV co-circulating in China: GI with a single genotype Ib and GII with eight genotypes.Genotype Ib is found to dominate China,particularly East and Central China and 34 natural recombination events were determined mostly from Ib and VII genotypes and highly involving the vaccine strains.A recombinant genotype XII isolated in 2019 seemed to emerge in Southern China.This study suggests that vaccinationinduced immune pressure might be driving the recombination among China NDVs,which might impact the security of NDV as an oncolytic virus and the safety of NDV live attenuated vaccines.Chapter 7 investigated Zika virus infection,one of the Blueprint Priority Diseases of WHO,which evolution in Southeast Asia countries is far from understood.Therefore,this chapter focused on screening the complete genomes collected between(1947-2021)and identified two genogroups,where Thailand strains were found to be highly variable and clustered into GI-2 close to Southeast Asia outbreak strains(Singapore 2016,the Philippines2012,and Cambodia 2010),independently of the Brazil outbreak viruses that clustered into GI-1 with French Polynesia outbreak strains 2013.This work determined for the first time that Thailand strains underwent recombination and that Thailand strains have the potential to recombine with Singapore and Cambodia strains,ringing bells on future severe ZIKV outbreaks in southeast Asia.