Species differences in circulation and inflammatory responses in children with common respiratory adenovirus infections

Abstract

Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but previous epidemiological studies lacked analysis of the characteristics of the inflammation. Consecutive patients <13 years old with acute febrile illness during a 2‐year period were tested. HAdV strains were isolated from nasopharyngeal swabs, and molecular identification was performed by hexon, fiber, and species‐specific PCR methods. Blood inflammatory markers, including the white blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected predominantly in 1‐year‐old, whereas B and E were in older ages. Species C and B had seasonal circulation patterns, but E was found in only one season during the 2‐year study period. The WBC count was highest in patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven kinds, including G‐CSF, IL‐6, and TNF‐α, were elevated in species C infections, whereas IL‐10 was lowest in species C. Species differences in inflammatory responses, especially regarding serum cytokines were described in common pediatric HAdV infections. Species C causes the strongest inflammatory responses in young children.

Recent advances in the detection of respiratory virus infection in humans

“…The genome contains the early expressed E1~E4 genes associated with replication of hAdV, intermediate gene of Ⅸ and Ⅳa2, and late region genes L1~L5 associated with the production of mature virions 60 . HAdV belongs to the Adenoviridae family, and it has been classified into seven species (A to G) with over 50 serotypes based on hexon and fiber protein characteristics, relative nucleic homology, immunochemical responses, biological properties, and phylogenetic relationships 35,61,62 . This subdivision has some clinical relevance, essentially because different hAdVs differ in tissue orientation and disease type.…”

Pediatric Infections by Human mastadenovirus C Types 2, 89, and a Recombinant Type Detected in Japan between 2011 and 2018

“…Adenovirus is a common source of respiratory infections among children [33]. Ad-2 and Human mastadenovirus B type 3 (Ad-3) are among the most frequently diagnosed agents reported on an annual basis [7,34]. The properties of such types leading to their frequent detection in infectious cases remain to be explained.…”

“…Pharyngeal specimens were collected from the pharynx of pediatric patients suspected of adenovirus respiratory tract infections and were tested as positive for adenovirus in screening tests with immunochromatographic kits [7]. The viral genomes were extracted from the throat swabs using the High Pure Viral Nucleic Acid Kit (Roche, Basel, Switzerland).…”

“…A multiplex-PCR that simultaneously targets Ad-1, -2, -5, -6, and -57 was employed to amplify the unique sequences within the fiber-coding regions and discriminated types based on amplicon size determined by agarose gel electrophoresis [7]. If multiple bands were detected for a single sample at the expected sizes, the sample was considered a co-infection.…”

“…HAdVs were isolated using the A549 cell line, as previously described [7]. There was a total of six isolates, which were chosen to include differentiable penton base regions and tested by neutralization analysis using rabbit antiserum against Ad-1, Ad-2, Ad-5, and Ad-6 (Denka-seiken, Tokyo, Japan).…”