The Immune Response to Respiratory Syncytial Virus Infection: Friend or Foe?

Department of Pediatrics, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, USA.
Clinical Reviews in Allergy & Immunology (Impact Factor: 5.46). 05/2008; 34(2):163-73. DOI: 10.1007/s12016-007-8033-2
Source: PubMed


The immune response to respiratory syncytial virus (RSV) infection has fascinated and frustrated investigators for decades. After adverse responses to early attempts at vaccination, it became popularly held that disease following infection was related to overly aggressive immune responses. However, recent data illustrate that severe forms of disease are related to inadequate, rather than hyperresponsive, adaptive immune reactions. Thus, recovery from primary (and perhaps later) RSV infection is dependent on the quality of innate immune responses. These findings should have enormous significance to the development of vaccines and antiviral compounds.

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    • "In vivo studies have demonstrated that viral and bacterial pathogens that are innocuous in WT mice can cause disease in IL-6-deficient mice (Jones et al., 2006; Ladel et al., 1997; Murphy et al., 2008; van der Poll et al., 1997). Infections with respiratory syncytial virus (RSV), a virus closely related to hMPV, demonstrated a positive correlation between high IL-6 levels and disease severity (Welliver, 2008). Moreover, hMPV induced a more severe disease in mice than RSV, and these results were, in part, associated with higher levels of host IL-6 (Huck et al., 2007). "
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    ABSTRACT: The host cytokine, interleukin-6 (IL-6), plays an important role in host defense and prevention of lung injury from various pathogens, making IL-6 an important mediator in the host's susceptibility to respiratory infections. The cellular response to IL-6 is mediated through a JAK/STAT3 signal transduction pathway. Human metapneumovirus (hMPV) is an important causative agent of viral respiratory infections known to inhibit the interferon-mediated activation of STAT1. However, little is known about the interactions between this virus and other STAT signaling cascades. Herein, we show that hMPV can attenuate the IL-6 mediated JAK/STAT3 signaling cascade in lung epithelial cells. HMPV inhibited a key event in this pathway by impeding the phosphorylation and nuclear translocation of STAT3 in A549 cells and in primary normal human bronchial epithelial cells. Further studies established that hMPV interrupted the IL-6 induced JAK/STAT pathway early in the signal transduction pathway by blocking the phosphorylation of JAK2. By antagonizing the IL-6 mediated JAK-STAT3 pathway, hMPV perturbed the expression of IL-6 inducible genes important for apoptosis, cell differentiation and growth. Infection with hMPV also differentially regulated the effects of IL-6 on apoptosis. Thus, hMPV regulation of these genes could usurp the protective roles of IL-6 and provide insight into an important element of viral pathogenesis.
    Preview · Article · Oct 2013 · Journal of General Virology
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    • "Clinical infection with hMPV and hRSV in humans occurs throughout life, despite the fact that most individuals sustain humoral immune responses to both hMPV (Ebihara et al., 2004; van den Hoogen et al., 2004) and hRSV (Baumeister et al., 2003; Ward et al., 1983). Whilst the cellular immune response following hRSV infection is well-understood in humans (Welliver, 2008) and in animal models (Hall et al., 1986; Rutigliano et al., 2005), in hMPV infection it is incompletely described. Similarities to hRSV suggest that CD8 + T cells are likely to be necessary to resolve hMPV infection in humans (Hall et al., 1986). "
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    ABSTRACT: Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory-tract infection in infants, the elderly and immunocompromised individuals. Virus-directed cellular immunity elicited by hMPV infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hRSV). In a murine model of acute lower respiratory-tract infection with hMPV, we demonstrate the accumulation of gamma interferon (IFN-gamma)-producing CD8+ T cells in the airways and lungs at day 7 post-infection (p.i.), associated with cytotoxic T lymphocytes (CTLs) directed to an epitope of the M2-1 protein. This CTL immunity was accompanied by increased pulmonary expression of Th1 cytokines IFN-gamma and interleukin (IL)-12 and antiviral cytokines (IFN-beta), as well as chemokines Mip-1alpha, Mip-1beta, Mig, IP-10 and CX3CL1. There was also a moderate increase in Th2-type cytokines IL-4 and IL-10 compared with uninfected mice. At 21 days p.i., a strong CTL response could be recalled from the spleen. A similar pattern of CTL induction to the homologous M2-1 CTL epitope of hRSV, and of cytokine/chemokine induction, was observed following infection with hRSV, highlighting similarities in the cellular immune response to the two related pathogens.
    Preview · Article · May 2010 · Journal of General Virology
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    ABSTRACT: Lung surfactant protein A (SP-A) has a central role in host defense mediated by the interaction of surface carbohydrates of inhaled pathogens with the lectin domains of SP-A. Respiratory syncytial virus (RSV), the most important viral pathogen of neonates and infants, encodes a highly glycosylated attachment protein, G. Binding studies were performed with G-protein from RSV (human, A2 strain) and human SP-A. The effect of SP-A on the interaction between RSV and host cells was determined by two methods: an infectivity study with monolayers of Hep-2C cells and by interleukin-8 (IL-8) release from buffy coat (BC) cells. SP-A binds to RSV G-protein in a concentration-dependent manner that is inhibitable by both ethylenediamine tetraacetic acid (EDTA) and mannan, indicating that binding is through the carbohydrate recognition domain of the SP-A and a carbohydrate moiety of the G-protein. The level of RSV infection of Hep-2C cells increases with increasing concentrations of SP-A. The amount of IL-8 released by BC cells in the presence of RSV is increased with SP-A concentrations of 2.9 microg/mL or greater. Our results show that SP-A enhances the attachment of RSV and subsequent entry into host cells. The effect of SP-A on viral uptake by epithelial cells and macrophage may determine both innate and adaptive immune responses to RSV.
    No preview · Article · Feb 2000 · Viral Immunology
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