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Circulation of a novel pattern of infections by enteric adenovirus serotype 41 among children below 5 years of age in Kolkata, India.

ABSTRACT: Human adenovirus of strains subgenus F (AdV F) are the most common strains detected in acute gastroenteritis cases in developing countries. Subgenus F is represented by AdV serotype 40 (AdV-40) and AdV-41. Most of the reports have described the predominance of AdV-41 in acute gastroenteritis cases. To gain insight into the epidemiology and genetic variation of AdV-41 strains, we analyzed 1,053 stool specimens from children with diarrhea. Among them, 42 (4.0%) and 56 (5.3%) were positive for enteric adenovirus 40/41 by enzyme-linked immunosorbent assay (ELISA) and PCR, respectively. For 1,305 asymptomatic children, 9 (0.7%) and 22 (1.7%) samples were positive for enteric adenovirus 40/40 by ELISA and PCR, respectively. The age distribution revealed a higher frequency (90%) in children <24 months of age. AdV F infection was observed at a low frequency throughout the year, with an increased incidence occurring during February and March. Sequence analysis of one to three hypervariable regions (HVRs) of the hexon genes of 16 representative AdV-41 strains in this study confirmed circulation of a unique strain with genomic type cluster 1 (GTC1)/GTC2. However, sequence analysis of the fiber genes of these strains confirmed 15 amino acid deletions from the 15th repeat motif of the shaft region. The existence of two GTCs reflects the accumulation of amino acid mutations in the HVR of the hexon gene. The novel AdV-41 strain might follow the same infection pattern as AdV-40. There is no significant variation in the sequences of hexon and fiber genes among strains from symptomatic and asymptomatic children. Our data confirm the circulation of an AdV-41 strain with a novel pattern in Kolkata, India, among children below 5 years of age.

SUBMITTER: Dey RS

PROVIDER: S-EPMC3043524 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Circulation of a novel pattern of infections by enteric adenovirus serotype 41 among children below 5 years of age in Kolkata, India.

Dey Rakhi Sharma RS Ghosh Santanu S Chawla-Sarkar Mamta M Panchalingam Sandra S Nataro James P JP Sur Dipika D Manna Byomkesh B Ramamurthy Thandavarayan T

Journal of clinical microbiology 20101201 2

Human adenovirus of strains subgenus F (AdV F) are the most common strains detected in acute gastroenteritis cases in developing countries. Subgenus F is represented by AdV serotype 40 (AdV-40) and AdV-41. Most of the reports have described the predominance of AdV-41 in acute gastroenteritis cases. To gain insight into the epidemiology and genetic variation of AdV-41 strains, we analyzed 1,053 stool specimens from children with diarrhea. Among them, 42 (4.0%) and 56 (5.3%) were positive for ente ...[more]

PMID: 21123530

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Project description:Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells in vivo This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.

Project description: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 a 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 hepatitis has not been resolved. Complete genomic HAdV-F41 sequences from thirty-two diagnostic specimens of the past 11 years (2011-22) were generated, all originating from gastroenteritis patients. Additionally, thirty-three complete HAdV-F41 genomes from GenBank were added to our phylogenetic analysis. Phylogenetic analysis of sixty-five 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 per cent. Lineage 2 included 53 isolates from 2000 to 2022, had an average nucleotide identity of 99.8 per cent, and split into two sublineages. Lineage 3, probably described for the first time in 2009, had a 45-nucleotide deletion in the long fibre gene and had evolved significantly in the short fibre and E3 region. Moreover, a recent Lineage 3 isolate from 2022 had a recombinant phylogeny of the short fibre gene. Fibres 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.

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Circulation of a novel pattern of infections by enteric adenovirus serotype 41 among children below 5 years of age in Kolkata, India.

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Circulation of a novel pattern of infections by enteric adenovirus serotype 41 among children below 5 years of age in Kolkata, India.

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