Molecular Phylogeny of human adenovirus type 41 lineages

Abstract

AbstractType 41 of human adenovirus species F (HAdV-F41) is a frequent aetiology of gastroenteritis in children, and nosocomial as well as kindergarten outbreaks have been frequently described. In contrast to other HAdV types, HAdV-F41 was not associated with life-threatening disseminated disease in allogeneic haematopoietic stem cell transplant (HSCT) recipients or any severe organ infections so far. Due to the limited clinical significance, the evolution of HAdV-F41 has not been studied in detail. Recently, HAdV-F41 has been associated with severe hepatitis in young children, and interest in HAdV-F41 has skyrocketed, although the aetiology of the hepatitis has not been resolved.Complete genomic HAdV-F41 sequences from 32 diagnostic specimens of the past 11 years (2011–2022) were generated, all originating from gastroenteritis patients. Additionally, 33 complete HAdV-F41 genomes from GenBank were added to our phylogenetic analysis.Phylogenetic analysis of 65 genomes indicated that HAdV-F41 evolved with three lineages co-circulating. Lineage 1 included the prototype ‘Tak’ from 1973 and six isolates from 2007 to 2017 with an average nucleotide identity of 99.3 %. Lineage 2 included 53 isolates from 2000 to 2022, had an average nucleotide identity of 99.8 %, and split into two sublineages. Lineage 3, probably described for the first time in 2009, had a 45nt deletion in the long fiber gene and had evolved significantly in the short fiber and E3 region. Moreover, a recent lineage 3 isolate from 2022 had a recombinant phylogeny of the short fiber gene. Fibers interact with cellular receptors and determine cellular tropism, whereas E3 gene products interfere with the immune recognition of HAdV infected cells.This in-depth study on the phylogeny of HAdV-F41 discovered significant evolution of recently described lineage 3 of HAdV-F41, possibly resulting in altered cellular tropism, virulence and pathophysiology.