Genomic analyses of human adenoviruses unravel novel recombinant genotypes associated with severe infections in pediatric patients

Abstract

Human adenoviruses (HAdVs) are highly contagious pathogens of clinical importance, especially among the pediatric population. Studies on comparative viral genomic analysis of cases associated with severe and mild infections due to HAdV are limited. Using whole-genome sequencing (WGS), we investigated whether there were any differences between circulating HAdV strains associated with severe infections (meningitis, sepsis, convulsion, sudden infant death syndrome, death, and hospitalization) and mild clinical presentations in pediatric patients hospitalized between the years 1998 and 2017 in a tertiary care hospital group in Bern, Switzerland covering a population base of approx. 2 million inhabitants. The HAdV species implicated in causing severe infections in this study included HAdV species C genotypes (HAdV1, HAdV2, and HAdV5). Clustering of the HAdV whole-genome sequences of the severe and mild cases did not show any differences except for one sample (isolated from a patient presenting with sepsis, meningitis, and hospitalization) that formed its own cluster with HAdV species C genotypes. This isolate showed intertypic recombination events involving four genotypes, had the highest homology to HAdV89 at complete genome level, but possessed the fiber gene of HAdV1, thereby representing a novel genotype of HAdV species C. The incidence of potential recombination events was higher in severe cases than in mild cases. Our findings confirm that recombination among HAdVs is important for molecular evolution and emergence of new strains. Therefore, further research on HAdVs, particularly among susceptible groups, is needed and continuous surveillance is required for public health preparedness including outbreak investigations.

An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat?

“…In the adult population, HAdVs that have been associated with disease in humans include species C (HAdV-1, HAdV-2 and HAdV-5), species B (HAdV-3 and HAdV-7), species E (HAdV-4) and species F (HAdV-41) predominantly in gastrointestinal pathology [ 78 , 79 , 80 ].…”

An Old Acquaintance. Could Adenovirus be our Next Pandemic Threat?

“…Noting that HAdV-4 occurs with low frequency in the general population (9,78,79) (Table 1). In the adult population, HAdVs that have been associated with disease in humans include species C (HAdV-1, HAdV-2, and HAdV-5), species B (HAdV-3 and HAdV-7), species E (HAdV-4) and the F species (HAdV-41) predominantly in gastrointestinal pathology (80,81,82).…”

“…After primary infection, species C genotypes can establish latent infections and are capable of long-term persistence in lymphoid cells (83,84). Therefore, asymptomatic people can shed infectious virus in the stool for many years (14,82).…”

“…It has been previously demonstrated that adenovirus has a higher mutation rate than another dsDNA (87). HAdVs have an unstable genome and are subject to genetic variations, being able to have mutations by insertion, substitution, or deletion of nucleotides; in addition, HAdVs can also undergo genomic recombination processes, first described during the 1970s and 1980s, between different viral strains in the same individual (82,88,89,90). These findings were confirmed by Dhingra et al, who demonstrated that multiple recombination events between E1 and E4 gene regions were possible, as part of the evolutionary process of HAdV-C (91).…”

Genomic Expedition: Deciphering Human Adenovirus Strains from the 2023 Outbreak in West Bengal, India: Insights into Viral Evolution and Molecular Epidemiology

“…On the other hand, HAdV16 and the recently identified HAdV50 are rarely detected and so are not well studied. A large amount of genetic variability is also observed in the HAdV3, 7, and 21 types [ 9 ].…”