Molecular Phylogeny of human adenovirus type 41 lineages
Type 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.