Molecular Phylogeny of human adenovirus type 41 lineages

Abstract

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, HAdVF41 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 (20112022) were generated, all originating from gastroenteritis patients. Additionally, 33 complete HAdVF41 genomes from GenBank were added to our phylogenetic analysis. Phylogenetic analysis of 65 genomes indicated that HAdV-F41 evolved with three lineages cocirculating. 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.

Suspected Adenovirus Causing an Emerging HEPATITIS among Children below 10 Years: A Review

“…Type F41 of the adenovirus is a common cause of severe diarrhea and diarrhea-related death in young children across the world. It was first discovered in the stool of a child with gastroenteritis in the Netherlands in 1973 [ 41 ]. Type F41 has also been known to cause severe gastroenteritis in children; it is characterized by fever, vomiting, and diarrhea [ 42 ].…”

Enteric adenovirus F41 genetic diversity comparable to pre-COVID-19 era: validation of a multiplex amplicon-MinION sequencing method

“…Sequences from [38] were excluded from further analysis due to large numbers of sequence gaps, in line with Gotting et al 2022 [24]. One HAdV-F41 genome sequence associated with AHUAC was generated at the Centre for Virus Research, Glasgow, UK [12] and kindly provided by Richard Orton and Emma Thomson.…”

“…Trees were visualised in iTOL [43]. F41 lineages were assigned based on the clusters and nomenclature from [24]. SimPlot++ v1.3 was used to generate similarity plots (SimPlots) using a window size of 500 bp, and a step size of 100 bp, using the Jukes-Cantor model [44].…”

“…sequences derived from AHUAC are highlighted on track 4. Lineage structure adapted from [24]. Phylogenies are also available to view on Microreact [45] https://microreact.org/project/bYhycuN63ZToY7348qJHbr-adenoviruscambridge.…”

“…Relatively little is known about HAdV-F41 genomic diversity in adults or children from the UK. Some data is available from immune compromised and hospitalised children from before the COVID-19 pandemic [22,23], and pre-and post-2020-21 samples are available from Germany [24]. It is therefore important to have access to HAdV-F41 genomes associated with gastrointestinal disease from the UK from the period after 2020-21 COVID-19 restrictions.…”