Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus-induced first wheezing episode in children

Pekka Hurme; Reetta Sahla; Beate Rückert; Tero Vahlberg; Riitta Turunen; Tytti Vuorinen; Mübeccel Akdis; Maria Söderlund-Venermo; Cezmi Akdis; Tuomas Jartti

doi:10.1002/clt2.12311

Human bocavirus 1 coinfection is associated with decreased cytokine expression in the rhinovirus-induced first wheezing episode in children

Clin Transl Allergy. 2023 Nov;13(11):e12311. doi: 10.1002/clt2.12311.

Authors

Pekka Hurme¹, Reetta Sahla¹, Beate Rückert², Tero Vahlberg³, Riitta Turunen^{1

4}, Tytti Vuorinen^{5

6}, Mübeccel Akdis², Maria Söderlund-Venermo⁷, Cezmi Akdis², Tuomas Jartti^{1

8

9}

Affiliations

¹ Department of Pediatrics and Adolescent Medicine, Turku University Hospital, University of Turku, Turku, Finland.
² Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
³ Department of Biostatistics, University of Turku, Turku, Finland.
⁴ New Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
⁵ Institute of Biomedicine, University of Turku, Turku, Finland.
⁶ Department of Clinical Microbiology, Turku University Hospital, Turku, Finland.
⁷ Department of Virology, University of Helsinki, Helsinki, Finland.
⁸ Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland.
⁹ Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland.

Abstract

Background: Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis.

Methods: Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years.

Results: The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group.

Conclusions: Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.

Keywords: bocavirus; bronchiolitis; cytokine; rhinovirus; virus; wheeze; wheezing.

Abstract

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