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      Blood MxA protein as a marker for respiratory virus infections in young children

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          Highlights

          • A prospective cohort of young children were studied for RTIs.

          • Blood MxA protein levels were elevated with symptomatic virus infections.

          • MxA response was demonstrated for rhinoviruses in clinical setting.

          • Immunization with live virus vaccine had a modest effect on MxA levels.

          Abstract

          Background

          Type I interferon induced MxA response can differentiate viral from bacterial infections, but MxA responses in rhinovirus or asymptomatic virus infections are not known.

          Objective

          To study MxA protein levels in healthy state and during respiratory virus infection of young children in an observational prospective cohort.

          Study design

          Blood samples and nasal swabs were collected from 153 and 77 children with and without symptoms of respiratory infections, respectively. Blood MxA protein levels were measured by an enzyme immunoassay and PCR methods were used for the detection of respiratory viruses in nasal swabs.

          Results

          Respiratory viruses were detected in 81% of symptomatic children. They had higher blood MxA protein levels (median [interquartile range]) than asymptomatic virus-negative children (695 [345–1370] μg/L vs. 110 [55–170] μg/L; p < 0.001). Within asymptomatic children, no significant difference was observed in MxA responses between virus-positive and virus-negative groups. A cut-off level of 175 μg/L had 92% sensitivity and 77% specificity for a symptomatic respiratory virus infection. Rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, coronavirus, and human metapneumovirus infections were associated with elevated MxA responses. Asymptomatic virus-negative children vaccinated with a live virus vaccine had elevated MxA protein levels (240 [120–540] μg/L), but significantly lower than children with an acute respiratory infection, who had not received vaccinations (740 [350–1425] μg/L; p < 0.001).

          Conclusion

          Blood MxA protein levels are increased in young children with symptomatic respiratory virus infections, including rhinovirus infections. MxA is an informative general marker for the most common acute virus infections.

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          Most cited references27

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          IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.

          We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.
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            Viruses and bacteria in the etiology of the common cold.

            Two hundred young adults with common colds were studied during a 10-month period. Virus culture, antigen detection, PCR, and serology with paired samples were used to identify the infection. Viral etiology was established for 138 of the 200 patients (69%). Rhinoviruses were detected in 105 patients, coronavirus OC43 or 229E infection was detected in 17, influenza A or B virus was detected in 12, and single infections with parainfluenza virus, respiratory syncytial virus, adenovirus, and enterovirus were found in 14 patients. Evidence for bacterial infection was found in seven patients. Four patients had a rise in antibodies against Chlamydia pneumoniae, one had a rise in antibodies against Haemophilus influenzae, one had a rise in antibodies against Streptococcus pneumoniae, and one had immunoglobulin M antibodies against Mycoplasma pneumoniae. The results show that although approximately 50% of episodes of the common cold were caused by rhinoviruses, the etiology can vary depending on the epidemiological situation with regard to circulating viruses. Bacterial infections were rare, supporting the concept that the common cold is almost exclusively a viral disease.
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              Rhinovirus-Associated Hospitalizations in Young Children

              Abstract Background. Rhinoviruses frequently cause the common cold but have not been considered important causes of acute respiratory hospitalizations in children. Methods. A population-based surveillance study was performed among children <5 years of age who were hospitalized with respiratory symptoms or fever and who resided within counties encompassing Nashville, Tennessee, or Rochester, New York, from October 2000 through September 2001. Data collected included questionnaires, nasal and throat swabs for viral culture and polymerase chain reaction testing, and chart review. Rates of rhinovirus-associated hospitalizations were calculated. Results. Of 592 children enrolled, 156 (26%) were rhinovirus positive, representing 4.8 (95% confidence interval [CI], 4.3–5.2) rhinovirus-associated hospitalizations/1000 children. Age-specific rates per 1000 children were 17.6 (95% CI, 14.9–20.6) for 0–5-month-olds, 6.0 (95% CI, 5.0–7.0) for 6–23-month-olds, and 2.0 (95% CI, 1.6, 2.4) for 24–59-month-olds (P<.01) Children with a history of wheezing/asthma had significantly more rhinovirusassociated hospitalizations than those without a history (25.3/1000 children [95% CI, 21.6–29.5/1000 children] vs. 3.1/1000 children [95% CI, 2.7–3.5/1000 children]). Conclusions. Rhinoviruses were associated with nearly 5 hospitalizations/1000 children <5 years of age and were highest in children with a history of wheezing/asthma.
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                Author and article information

                Contributors
                Journal
                J Clin Virol
                J. Clin. Virol
                Journal of Clinical Virology
                Elsevier B.V.
                1386-6532
                1873-5967
                18 November 2014
                January 2015
                18 November 2014
                : 62
                : 8-13
                Affiliations
                [a ]Department of Paediatrics, Turku University Hospital, Turku, Finland
                [b ]Turku Institute for Child and Youth Research, University of Turku, Turku, Finland
                [c ]Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland
                [d ]Immunogenetics Laboratory, University of Turku, Turku, Finland
                [e ]Virology Unit, National Institute of Health and Welfare, Helsinki, Finland
                [f ]Department of Virology, University of Turku, Turku, Finland
                Author notes
                [* ]Corresponding author at: Department of Virology, University of Turku, Kiinamyllynkatu 13, FI-20520 Turku, Finland. Tel.: +358 23337465; fax: +358 22513303. matti.waris@ 123456utu.fi
                Article
                S1386-6532(14)00426-0
                10.1016/j.jcv.2014.11.018
                7106481
                25542463
                6ead216e-3193-42a9-ad91-360babb5c2ee
                Copyright © 2014 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 4 September 2014
                : 30 October 2014
                : 8 November 2014
                Categories
                Article

                Microbiology & Virology
                mxa protein,respiratory virus infection,rhinovirus,rotavirus vaccine,interferon,steps study

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