Human Metapneumovirus Infection in Hospitalized Children

Holzemer, Nicholas F; Hasvold, Jennifer; Pohl, Kyle; Ashbrook, Matthew J; Meert, Kathleen L.; Quasney, Michael W.

doi:10.4187/respcare.07156

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…There are limited data on HMPV immune responses and pathogenesis in humans, primarily in young children [ 6 – 9 ]. Previous studies using young adult mouse HMPV models showed that CD8 + T cells help mediate viral clearance and protective immunity [ 10 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

et al. 2023

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Background Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. Results Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1−/− recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7− TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. Conclusions This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.

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Section: Introductionmentioning

confidence: 99%

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

et al. 2023

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“…It was first isolated from a pediatric patient in the Netherlands in 2001 [ 1 ]. It is also one of the most common viruses causing acute upper and lower respiratory tract infections in children, immunocompromised individuals, and elderly [ 2 – 5 ]. HMPV infection most commonly occurs in children below 2 years old [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Profiles and predictive value of cytokines in children with human metapneumovirus pneumonia

Xiang

Lin

Wang

et al. 2022

Virol J

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Background Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. Early innate immune response to HMPV is focused on induction of antiviral interferons (IFNs) and other pro-inflammatory cytokines that are critical for the formation of adaptive immune responses. To evaluate the predictive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV. Methods A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. 131 children infected with Influenza virus A (IVA) and 41 children infected with influenza virus B (IVB) were detected by RT-PCR assay in throat swabs. Results When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p < 0.001) and higher levels of IL-4 (p < 0.001), IL-6 (p = 0.001), IL-10 (p < 0.001), and IFN-γ (p < 0.001). Compared with patients diagnosed with IVA or IVB infection, HMPV-positive patients had significantly higher levels of IL-4 (p < 0.001 and < 0.001), IFN-γ (p < 0.001 and < 0.001), and TNF-α (p < 0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p = 0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p = 0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild symptoms and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI 0.526–0.829) and 0.658 (95% CI 0.506–0.809), respectively. Conclusion Our study indicated that difference in cytokine trends depending on the virus species. The levels of IL-4, TNF-α and IFN-γ were significantly distinguished in children infected with HMPV versus IVA and IVB. IL-6 and TNF-α may be helpful in assessing the severity and prognosis of HMPV infection.

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“…It was rst isolated from a pediatric patient in the Netherlands in 2001 [1]. It is also one of the most common viruses causing acute upper and lower respiratory tract infections in children, immunocompromised individuals, and elderly [2][3][4][5]. HMPV infection most commonly occurs in children below 2 years old [6].…”

Section: Introductionmentioning

confidence: 99%

Profiles and Predictive Value of Cytokines in Children with Human Metapneumovirus Pneumonia

Xiang

Lin

Wang

et al. 2022

Preprint

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Background: Human metapneumovirus (HMPV) is an important cause of respiratory tract infections in young children. To evaluate the predicitive value of Th1/Th2 cytokines which include IL-2, IL-4, IL-6, IL-10, INF-γ and TNF-α in pneumonia caused by HMPV. Methods: A retrospective study was performed among 59 pneumonia pediatric patients with HMPV infection and 33 healthy children as the control cohort, which was detected by the immunofluorescence assay, and the Th1/Th2 cytokines were measured by flow cytometry. Results: When compared with the healthy children, children who were infected with HMPV pneumonia had a significantly lower level of IL-2 (p<0.001) and higher levels of IL-4 ((p<0.001), IL-6 (p=0.001), IL-10 (p<0.001), and IFN-γ (p<0.001). Compared with patients diagnosed with influenza virus A (IVA) or influenza virus B (IVB) infections, HMPV-positive patients had significantly higher levels of IL-4 (p<0.001 and <0.001), IFN-γ (p<0.001 and <0.001), and TNF-α (p<0.001 and 0.016). Moreover, compared with IVA patients, HMPV-positive patients had a significantly lower level of IL-6 (p=0.033). Finally, when comparing cytokine levels among the patients with HMPV pneumonia, IL-6 and TNF-α levels were found to be significantly higher in the severe group than the mild group (p=0.027 and 0.049). The IL-6 and TNF-α were used to differentiate between mild and severe symptoms in children diagnosed with HMPV pneumonia with an AUC of 0.678 (95% CI, 0.526-0.829) and 0.658 (95% CI, 0.506-0.809), respectively.Conclusions: Our study indicates that IL-2, IL-4, IL-6, IL-10, and IFN-γ may be a reference for auxiliary diagnose HMPV pneumonia in children. IL-4, TNF-α, and IFN-γ may serve as biomarkers to distinguish HMPV from IVA and IVB, whereas IL-6 may be able to differentiate between HMPV and IVA. IL-6 and TNF-α may be used to assessment of severity and prognosis of HMPV infection.

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Human Metapneumovirus Infection in Hospitalized Children

Cited by 5 publications

References 28 publications

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

Terminally exhausted CD8+ T cells contribute to age-dependent severity of respiratory virus infection

Profiles and predictive value of cytokines in children with human metapneumovirus pneumonia

Profiles and Predictive Value of Cytokines in Children with Human Metapneumovirus Pneumonia

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