https://orcid.org/0000-0002-2088-0629
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ABSTRACT
Rhinoviruses (RV) are the major cause of chronic obstructive pulmonary disease and are associated with exacerbation development as well as community-acquired pneumonia in children, leading to substantial morbidity, mortality, and hospital admission. Here we have examined how changes at the amino terminal of the conserved VP4 epitope of different RV serotypes may affect pulmonary cytokine and chemokine responses and disease severity. Samples positive for rhinovirus were used for genetic characterization, followed by profiling gene expression of pulmonary Th1 and Th2 cytokines/chemokines by RT-PCR arrays. Genetic sequencing and homology 3D modeling revealed changes at the amino terminal of the conserved viral protein 4 (VP4) epitope in the RV-A101 serotype, especially serine at several positions that are important for interactive binding with the host immune cells. We found dysregulation of pulmonary gene expression of Th1- and Th2-related cytokines and chemokines in RV-A 101 and RV-C 8 pneumonia patients. These findings might contribute to a better understanding of RV immunity and the potential mechanisms underlying the pathogenesis of severe RV infections, but further functional studies are needed to confirm the causal relationship.
List of abbreviations
| CDHR3 | = | cadherin-related family member 3 |
| CD4 | = | Cluster of Differentiation 4 |
| Ct | = | Cycle-threshold values |
| CXR | = | Chest radiograph |
| GGO | = | ground glass opacity |
| GTR | = | General time reversible model |
| ICAM-1 | = | intercellular adhesion molecule 1 |
| ICU | = | Intensive care unit |
| IFN-γ | = | Interferon gamma |
| IL-18 | = | interleukin or interferon-gamma-inducing factor 18 |
| LDLR | = | low-density lipoprotein receptor |
| OPD | = | outpatient department |
| RT-PCR | = | reverse transcription PCR |
| RVs | = | Rhinoviruses |
| Th1 | = | T helper cell type 1 |
| Th2 | = | T helper cell type 2 |
| TNFα | = | Tumor Necrosis Factor alpha |
| VP4 | = | Viral Protein 4 |
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
A.N, A.Z, and B.A contributed to study design, data analysis, results discussion, and manuscript writing and review; A.N, H.S.A, and M.E.H conducted the experimental work; W.A contributed to data analysis and manuscript writing; A.S.A contributed to sample and data collection; A.N and W.A performed results discussion and clinical interpretation; M.U.M and I.Y contributed to radiology reports collection and data analysis; A.Z. contributed to Study design, clinical analysis of data, results discussion, manuscript writing and review. All authors read, reviewed, discussed, and agreed to their individual contributions ahead of this time.
Data availability statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Institutional review board statement
The institutional review board at King Fahad Medical City reviewed and approved the study protocol (IRB Log No. 19–565 approved on 12 November 2019). When the COVID-19 pandemic started, the collection of samples stopped on the 2nd of March 2020 due to non-COVID research embargo. We resumed the patient enrollment and sample collection on the 16th of September 2020 until 25th of January 2021.
Informed consent statement
Signed informed consent to participate was not required and was waived by IRB since only anonymized left‐over specimens were retrospectively obtained without any personally identifiable information. Permissions from the parent/guardian of the patients were obtained according to the policy of King Fahad Medical City.