Collins, P.L. & Graham, B.S. Viral and host factors in human respiratory syncytial virus pathogenesis. J. Virol. 82, 2040-2055

NIAID, NIH, 50 South Drive, MSC 8007, Bethesda, MD 20892, USA.
Journal of Virology (Impact Factor: 4.65). 04/2008; 82(5):2040-55. DOI: 10.1128/JVI.01625-07
Source: PubMed

ABSTRACT Human respiratory syncytial virus (RSV) was first isolated in 1956 from a laboratory chimpanzee with upper respiratory tract disease (for general reviews, see references 21, 57, 102, and 145). RSV was quickly determined to be of human origin and was shown to be the leading worldwide viral agent of serious pediatric respiratory tract disease. In a 13-year pro- spective study of infants and children in the United States, RSV was detected in 43%, 25%, 11%, and 10% of pediatric hospitalizations for bronchiolitis, pneumonia, bronchitis, and croup, respectively (110). Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by 2 years of age. The rate of hospitalization for primary infection is approximately 0.5% but can vary by situation and ethnic group and can be as high as 25% (77). RSV also is a significant cause of morbidity and mortality in the elderly, with an impact approaching that of nonpandemic influenza virus (39). RSV readily infects severely immunocom- promised individuals, most notably allogeneic bone marrow transplant recipients, causing high mortality. RSV also makes a substantial contribution to upper respiratory tract disease in individuals of all ages (59, 65). Globally, the World Health Organization estimates that RSV causes 64 million infections and 160,000 deaths annually (Initiative for Vaccine Research: respiratory syncytial virus, World Health Organization (http: //,

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    • "There is no commercial vaccine to prevent infection with HRSV (Collins & Melero 2011, Graham 2011). Important factors should be considered to explain unsuccessful attempts in the development of effective vaccine against HRSV, such as the immaturity of the immune system, the suppressor effect of the mother's antibody in the first years of life (Collins & Graham 2008, Graham 2011) and viral genetic variability (Peret et al. 1998). The most immunogenic proteins are G (adhesion) and F (fusion), which show the highest rates of amino acid variability in their outer portions (Ogra 2004). "
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    ABSTRACT: Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.
    Memórias do Instituto Oswaldo Cruz 02/2015; DOI:10.1590/0074-02760140299 · 1.57 Impact Factor
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    • "Although the identification of HRSV as an important cause of bronchiolitis in infants was made more than 55 years ago, there is still no licensed vaccine for this important respiratory pathogen (Collins & Graham, 2008). Most attempts to develop such a vaccine aim at inducing neutralizing antibodies directed against the major surface proteins, F and G (Graham, 2011). "
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    ABSTRACT: Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcγRI and FcγRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection.
    EMBO Molecular Medicine 10/2014; 6(11). DOI:10.15252/emmm.201404005 · 8.25 Impact Factor
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    • "In conclusion, severe RSV infections were in part influenced by the emergence of strain NA1. However, in our experience and according to other authors, we postulate that in infants younger than 6 months of age, the clinical severity of RSV infection is mainly due to the profile of immune response that is induced by the virus in each individual child [1] [14] [25]. In contrast, in very young infants infected by HRV, the relative immaturity of the immune system may avoid the induction of an intense inflammatory response, as it is seen in older infants or in atopic individuals throughout life. "
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    ABSTRACT: Background Respiratory syncytial virus (RSV) and rhinovirus (HRV) are the main cause of acute lower respiratory tract infections (ALRTIs) in infants. Viral and host-related risk factors for severe disease have also not been clearly established. Objective to assess whether certain viral features of RSV and, or HRV are associated with severe ALRTI. Study design: RSV and HRV were studied in nasopharyngeal samples of infants by immunofluorescence, Luminex® and/or real-time RT-PCR assays. Quantitation and genotyping of RSV and HRV by PCR were done. Results Of 124 virus positive specimens, 74 (59.7%) had RSV; 22 (17.7%) HRV and 28 (22.6%) RSV-HRV co-infection. Hospitalization was required in 57/74 RSV infants (77.0%); in 10/22 HRV cases (45.5%) (p= 0.006) and in 15/28 co-infected by both viruses (53.6%) (p= 0.003). Severe cases were 33/74 (44.6%) RSV infections, 2/22 HRV cases (9.1%), (p < 0.002) and 6/28 (21.4%) patients co-infected by RSV-HRV (p <0.026). Three genotypes (NA1, B7, B9) of RSV circulated during the study. In 33 severe infants, NA1 was detected in 19 cases (57.6%); B7 in 13 (39.4%) and B9 in 1 (3.0%) (p < 0.01; OR = 10.0). RSV loads were similar between outpatients and hospitalized infants (p = 0.7) and among different severities (p = 0.7). NA1 loads were higher than other strains (p = 0.049). Three geno-groups of HRV circulated homogeneously. Conclusion in very young infants, RSV cause more severe disease than HRV. Co-infection does not increase the severity of illness. NA1 RSV genotype was associated with major frequency of hospitalization, severe respiratory disease and higher viral load.
    Journal of Clinical Virology 09/2014; 61(1). DOI:10.1016/j.jcv.2014.06.004 · 3.47 Impact Factor
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