Clinical Features, Replication Competence, and Innate Immune Responses of Human Adenovirus Type 7 Infection

Area of Science:

• Virology
• Pediatric Infectious Diseases
• Immunology

Background:

• Epidemiologic data indicate a strong association between severe or fatal adenoviral disease in children and human adenovirus (HAdV) type 7.
• The precise mechanisms driving the pathogenesis of severe HAdV-7 disease remain inadequately understood.

Purpose of the Study:

• To compare the replication kinetics and host response to HAdV-3 and HAdV-7 infections.
• To investigate the correlation between viral load, cytokine profiles, and clinical severity in children infected with HAdV-7 versus HAdV-3.

Main Methods:

• Ex vivo human lung tissue cultures were used to assess HAdV-3 and HAdV-7 replication.
• Cytokine and chemokine levels were measured using multiplex immunoassay in hospitalized children.
• Adenovirus DNA in serum was quantified by Taqman real-time PCR in HAdV-7 (n=65) and HAdV-3 (n=48) infected children.

Main Results:

• HAdV-7 was more prevalent in 2018, while HAdV-3 predominated in 2014-2016. Severe pneumonia incidence was significantly higher in HAdV-7 cases (30.1%) compared to HAdV-3 cases (4.5%).
• HAdV-7 demonstrated more efficient replication ex vivo. Significantly elevated levels of Interferon-induced protein 10, Interleukin-6, and Monocyte Chemoattractant Protein 1 were observed in HAdV-7 infected children.
• Adenovirus DNA was detected in 40% of HAdV-7 infected children versus 4.2% of HAdV-3 infected children, with viremia strongly correlating with severe clinical presentations.

Conclusions:

• The severe disease associated with HAdV-7 likely stems from its high replication efficiency and the resulting hyperinflammatory host response.
• Detection of adenovirus DNA in the blood (viremia) may serve as a valuable biomarker for identifying children at high risk of severe HAdV-7 disease.