Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection

Mejías, Asunción; Dimo, Blerta; Suárez, Nicolás M.; García, Carme Salvador; Suarez-Arrabal, M. Carmen; Jartti, Tuomas; Blankenship, Derek; Jordán-Villegas, Alejandro; Ardura, Monica I.; Xu, Zhaohui; Banchereau, Jacques; Chaussabel, Damien; Ramilo, Octavio

doi:10.1371/journal.pmed.1001549

Cited by 274 publications

(334 citation statements)

References 38 publications

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“…Clinically, these data suggest that the inhibitory effect of Siglec‐1 on T cells mainly affects memory T cells during reinfections. Mejias et al also observed an inhibitory effect of RSV on T cells during RSV infections in infants 30. Future research should determine at what time after birth this inhibitory effect takes place, because our data indicate that in certain circumstances Siglec‐1‐dependent inhibition of T cells is not present directly after birth.…”

Section: Discussionsupporting

confidence: 54%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

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Section: Discussionsupporting

confidence: 54%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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“…The host initiates an innate immune response to virus infection to promote antiviral gene expression, including interferon production (52,53). To dissect the effect of IFN-␤ production and direct detection of viral RNA on NLRC5 expression, we then transfected Vero cells with viral RNA.…”

Section: Rsv Infection Upregulatesmentioning

confidence: 99%

Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells

Guo

Liu

Shi

et al. 2015

J Virol

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Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. The host antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We show here that RSV infection upregulates major histocompatibility complex class I (MHC-I Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children, causing bronchiolitis and pneumonia in infants and young children worldwide. Due to the highly infectious nature of the virus, roughly two-thirds of children are infected by their first birthday, and this reaches essentially 100% by the age of 2 (1, 2). RSV infection is a leading cause of infant hospitalization due to bronchiolitis (2, 3). In the United States alone, an estimated 2.1 million children under 5 years of age with RSV infection require medical attention each year (4). Importantly, lower respiratory tract infection by RSV early in life is a risk factor for persistent wheezing and asthma in later life (5, 6). There are no RSV vaccines available to prevent childhood infection. These factors create an urgent need to understand the mechanisms of RSV disease, the molecular mechanisms associated with immunoregulation, and the downstream association between RSV infection and allergic asthma.RSV belongs to the subfamily Pneumovirinae of the paramyxoviruses. A negative-sense, single-stranded RNA virus with a genome of approximately 15,000 nucleotides (7), the virus can infect a broad range of cells. In patients, however, infection is normally highly restricted to the superficial cells of the respiratory epithelium, the ciliated cells of the small bronchioles, and pneumocytes in the alveoli (8-10). Infection is initiated by cell surface binding via proteoglycans (11), followed by nucleolin-mediated fusion for RSV cell entry (9, 12) and infection. In response, the host initiates an early innate immune response at the site of infection. Receptors of innate immune recognition, like Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I), which are involved in detection of viral RNA, promote the activation of antiviral immunity and cytokine production, as well as the recruitment of proinflammatory cells (10,(13)(14)(15)(16). This increased expression of inflamma-

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“…A 30-gene classifier developed in this setting separated symptomatically virally infected and uninfected volunteers with 93% accuracy, and it was subsequently validated in a separate cohort of patients, where it classified naturally acquired infections as being either viral or bacterial infections with 80% accuracy (17). Gene expression-based classifiers have also been shown to differentiate between specific viral etiologies, as demonstrated by a 70-gene RSV transcriptional profile that successfully separated infants with RSV lower respiratory tract infection from those with HRV or influenza virus infection with 94% sensitivity and 98% specificity (18). In addition to successfully distinguishing viral and bacterial infections, a gene expression-based classifier of viral infection has also demonstrated the ability to diagnose subjects very early, during the presymptomatic phase, and to allow eventual severity prediction (9).…”

Section: Current Gene Expression-based Disease Classifiersmentioning

confidence: 99%

Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases

et al. 2017

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Emerging pandemic infectious threats, inappropriate antibacterial use contributing to multidrug resistance, and increased morbidity and mortality from diagnostic delays all contribute to a need for improved diagnostics in the field of infectious diseases. Historically, diagnosis of infectious diseases has relied on pathogen detection; however, a novel concept to improve diagnostics in infectious diseases relies instead on the detection of changes in patterns of gene expression in circulating white blood cells in response to infection. Alterations in peripheral blood gene expression in the infected state are robust and reproducible, yielding diagnostic and prognostic information to help facilitate patient treatment decisions.

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Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection

Abstract: In this study, Mejias and colleagues found that specific blood RNA profiles of infants with RSV LRTI allowed for specific diagnosis, better understanding of disease pathogenesis, and better assessment of disease severity. Please see later in the article for the Editors' Summary

Cited by 274 publications

References 38 publications

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells

Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases

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