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T-Cell Responses in Adults During Natural Respiratory Syncytial Virus Infection.

ABSTRACT: Background:The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum. Methods:Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry. Results:There were no significant age-related differences in frequency of CD4+ T cells synthesizing interferon (IFN)?, interleukin (IL)2, IL4, IL10, or tumor necrosis factor (TNF)? or in CD8+IFN?+ T cells. IL4+CD4+ T-cell numbers were low, as were IL13 and IL17 responses. However, in univariate analysis, CD4 T-cell IFN?, IL2, IL4, IL10, and TNF? responses and CD8+IFN?+ T cells were significantly increased with more severe illness requiring hospitalization. In multivariate analysis, viral load was also associated with increased T-cell responses. Conclusions:We found no evidence of diminished RSV-specific CD4 or CD8 T-cell responses in adults infected with RSV. However, adults with severe disease seemed to have more robust CD4 and CD8 T-cell responses during infection, suggesting that disease severity may have a greater association with T-cell responses than age.

SUBMITTER: Roumanes D

PROVIDER: S-EPMC6049038 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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T-Cell Responses in Adults During Natural Respiratory Syncytial Virus Infection.

Roumanes D D Falsey A R AR Quataert S S Secor-Socha S S Lee F E-H FE Yang H H Bandyopadhyay S S Holden-Wiltse J J Topham D J DJ Walsh E E EE

The Journal of infectious diseases 20180701 3

<h4>Background</h4>The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum.<h4>Methods</h4>Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry.<h4>Results</h4>There were no ...[more]

PMID: 29920599

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Project description:Respiratory syncytial virus (RSV) infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of type I and III interferons (IFNs) and proinflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV). A549 cells were highly permissive, whereas BEAS-2B cells restricted infection to individual cells or small foci. After infection, A549 cells expressed higher levels of IFN-β-, IFN-λ-, and NF-κB-inducible proinflammatory cytokines. In contrast, BEAS-2B cells expressed higher levels of antiviral interferon-stimulated genes, pattern recognition receptors, and other signaling intermediaries constitutively and after infection. Transcriptome analysis revealed that constitutive expression of antiviral and proinflammatory genes predicted responses by each cell line. These two cell lines provide a model for elucidating critical mediators of local control of viral infection in respiratory epithelial cells.IMPORTANCE Airway epithelium is both the primary target of and the first defense against respiratory syncytial virus (RSV). Whether RSV replicates and spreads to adjacent epithelial cells depends on the quality of their innate immune responses. A549 and BEAS-2B are alveolar and bronchial epithelial cell lines, respectively, that are often used to study RSV infection. We show that A549 cells are permissive to RSV infection and express genes characteristic of a proinflammatory response. In contrast, BEAS-2B cells restrict infection and express genes characteristic of an antiviral response associated with expression of type I and III interferons. Transcriptome analysis of constitutive gene expression revealed patterns that may predict the response of each cell line to infection. This study suggests that restrictive and permissive cell lines may provide a model for identifying critical mediators of local control of infection and stresses the importance of the constitutive antiviral state for the response to viral challenge.

Project description:ImportanceLittle is known about the burden and outcomes of respiratory syncytial virus (RSV)-positive acute respiratory infection (ARI) in community-dwelling older adults.ObjectiveTo assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults.Design, setting, and participantsThis was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI.ExposureRSV-positive and -negative ARI.Main outcomes and measuresRSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed.ResultsIn this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, -16.7 [95% CI, -31.8 to -1.8]; fatigue, -8.4 [95% CI, -14.3 to -2.4]; and difficulty in social functioning, -11.9 [95% CI, -19.8 to -4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: -4.0 [95% CI, -8.5 to -1.3]; difficulty in social functioning, -5.8 [95% CI, -10.3 to -1.3]; and limitation due to emotional problem, -7.0 [95% CI, -12.7 to -1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, -4.4 [95% CI, -7.3 to -1.5]; difficulty in social functioning, -5.2 [95% CI, -8.7 to -1.7] and limitation due to emotional problem, -5.7 [95% CI, -10.7 to -0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities.Conclusions and relevanceIn this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Dataset Information

T-Cell Responses in Adults During Natural Respiratory Syncytial Virus Infection.

Publications

T-Cell Responses in Adults During Natural Respiratory Syncytial Virus Infection.

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