Genetic characterization of human adenoviruses in patients using metagenomic next-generation sequencing in Hubei, China, from 2018 to 2019

Abstract

ObjectivesThis study aimed to characterize the genomic epidemiology of human adenoviruses (HAdVs) in Hubei, China, using metagenomic next-generation sequencing (mNGS).MethodsIn total, 25 HAdV-positive samples collected from 21 pediatric patients were sequenced and subjected to mNGS using the NextSeq 550 and GenoLab M sequencing platforms. The metagenomic data were assembled de novo for molecular typing, phylogenetic and recombination analyzes.ResultsWe assembled 50 HAdV genomes, 88% (22/25) genomes from GenoLab M, and 84% (21/25) genomes from NextSeq 550 have perfect alignments to reference genomes with greater than 90%. The most fully assembled 25 genomes were categorized into 7 HAdV genotypes, the most abundant of which were HAdV-B3 (9/25) and HAdV-C2 (6/25). Phylogenetic analyzes revealed that the newly isolated HAdV-B3 strains diverged into separate clusters according to their genotypes. Vigilance is needed that HAdV-B3 isolates have begun to form new distinct clusters. High nucleotide identity was observed in the whole genome level within the same HAdV genotypes, while marked differences of three capsid genes across HAdV genotypes were noted. The high nucleotide diversity regions were concordant with the reported hypervariable regions. Further, three recombinant strains were identified: S64 and S71 originated from the parental strains HAdV-B14 and HAdV-B11, and S28 originated from HAdV-C1, HAdV-C5, and HAdV-CBJ113. GenoLab M and NextSeq 550 showed comparable performance with respect to data yield, duplication rate, human ratio, and assembly completeness.ConclusionThe sequencing quality and assembly accuracy showed that mNGS assembled genomes can be used for subsequently HAdV genotyping and genomic characterization. The high nucleotide diversity of capsid genes and high frequency of recombination events has highlighted the necessity for HAdV epidemiological surveillance in China.

Genotypes and Phylogenetic Analysis of Human Adenovirus in Hospitalized Pneumonia and Influenza-Like Illness Patients in Jiangsu Province, China (2013-2021)

“…HAdVE4 has been previously classified as two separate evolutionary lineages, prototype (p)-like and a-like, and the mutation rate of a-like was higher, indicating that it has a wider host range and stronger transmission ability. 16 , 48 HAdVE4 caused febrile acute respiratory disease outbreaks in the military and are also circulating in civilian population. Patients infected with HAdVE4 are at increased risk of developing severe disease.…”

“… 14 Recombination is the main driver of HAdV evolution and the emergence of new pathogenic strains. 15 , 16 Influenza and pneumonia are common respiratory diseases that seriously affect human health. 17 , 18 Influenza-like illness (ILI) and pneumonia can be caused by a variety of viral and bacterial pathogens, including adenovirus.…”

Innate Immune Response to Viral Vectors in Gene Therapy

“…Additionally, it exhibits suboptimal infection efficiencies in certain cancer contexts. Ad is classified into seven types, A-G. To date, a cumulative count of 111 HAdV genotypes has been documented and categorized into seven species (A-G), all of which have the potential to infect individuals across various age groups, albeit only a limited subset leading to severe infections [30]. These vectors are mainly derived from Ad serotype 2 (Ad2) and Ad serotype 5 (Ad5) of species C, with Ad5 being the most widespread [31].…”