Martin L Moore

Children's Healthcare of Atlanta, Atlanta, Georgia, United States

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Publications (46)220.92 Total impact

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    ABSTRACT: A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the two most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTI) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we will systematically review the evidence linking early life RSV and RV LRTI with asthma inception and whether they could therefore be targets for primary prevention efforts.
    American Journal of Respiratory and Critical Care Medicine 11/2014; · 11.04 Impact Factor
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    ABSTRACT: Human respiratory syncytial virus (RSV) lower respiratory tract infection can result in inflammation and mucus plugging of airways. RSV strain A2-line19F induces relatively high viral load and mucus in mice. The line19 fusion (F) protein harbors five unique residues compared to the non-mucus-inducing strains A2 and Long, at positions 79, 191, 357, 371, and 557. We hypothesized that differential fusion activity is a determinant of pathogenesis. In a cell-cell fusion assay, line19 F was more fusogenic than Long F. We changed the residues unique to line 19 F to the corresponding residues in Long F and identified residues 79 and 191 together as responsible for high fusion activity. Surprisingly, mutation of residues 357 or 357 with 371 resulted in gain of fusion activity. Thus, we generated RSV F mutants with a range of defined fusion activity and engineered these into recombinant viruses. We found a clear, positive correlation between fusion activity and early viral load in mice, however, we did not detect a correlation between viral loads and levels of airway mucin expression. The F mutant with the highest fusion activity, A2-line19F-K357T/Y371N, induced high viral loads, severe lung histopathology, and weight loss, but did not induce high levels of airway mucin expression. We defined residues 79/191 as critical for line19 F fusion activity and 357/371 as playing a role in A2-line19F mucus induction. Defining the molecular basis of the role of RSV F in pathogenesis may aid vaccine and therapeutic strategies aimed at this protein.
    Journal of virology. 10/2014;
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    ABSTRACT: Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants and a high priority for vaccine development. We previously reported that RSV virus-like particles (VLPs) expressing either the fusion (F) or attachment (G) glycoprotein could confer protection against RSV challenge in BALB/c mice. Here, we tested the hypothesis that RSV VLP vaccine efficacy can be enhanced by mixing RSV VLP F and RSV VLP G, and we analyzed host responses to these RSV VLPs. Mice were immunized with VLP F, VLP G, or VLP F + VLP G. Lung viral loads in BALB/c mice following RSV strain A2-line19F challenge were lower in mice vaccinated with RSV VLP F + VLP G compared to VLP F- or VLP G-vaccinated mice. Vaccination with VLP F or VLP F + VLP G induced similar levels of neutralizing antibodies. The enhanced protection against RSV challenge induced by vaccination with RSV VLP F + VLP G correlated with CD8 T cells producing T helper type 1 cytokines. VLP G vaccination alone followed by challenge resulted in immunopathology similar to formalin-inactivated RSV vaccination and RSV challenge. Taken together, mixed VLP F + VLP G provided a high level of protection against RSV without vaccine-induced immunopathology, but VLP G vaccination enhanced disease when used alone.
    Antiviral research. 09/2014;
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    ABSTRACT: Background Some investigators find a deficiency in IFN production from airway epithelial cells infected with human rhinovirus in asthma, but whether this abnormality occurs with other respiratory viruses is uncertain. Objective To assess the effect of influenza A virus (IAV) and respiratory syncytial virus (RSV) infection on IFN production and viral level in human bronchial epithelial cells (hBECs) from subjects with and without asthma. Methods Primary-culture hBECs from subjects with mild to severe asthma (n = 11) and controls without asthma (hBECs; n = 7) were infected with live or ultraviolet-inactivated IAV (WS/33 strain), RSV (Long strain), or RSV (A/2001/2-20 strain) with multiplicity of infection 0.01 to 1. Levels of virus along with IFN-β and IFN-λ and IFN-stimulated gene expression (tracked by 2′-5′-oligoadenylate synthetase 1 and myxovirus (influenza virus) resistance 1 mRNA) were determined up to 72 hours postinoculation. Results After IAV infection, viral levels were increased 2-fold in hBECs from asthmatic subjects compared with nonasthmatic control subjects (P < .05) and this increase occurred in concert with increased IFN-λ1 levels and no significant difference in IFNB1, 2′-5′-oligoadenylate synthetase 1, or myxovirus (influenza virus) resistance 1mRNA levels. After RSV infections, viral levels were not significantly increased in hBECs from asthmatic versus nonasthmatic subjects and the only significant difference between groups was a decrease in IFN-λ levels (P < .05) that correlated with a decrease in viral titer. All these differences were found only at isolated time points and were not sustained throughout the 72-hour infection period. Conclusions The results indicate that IAV and RSV control and IFN response to these viruses in airway epithelial cells is remarkably similar between subjects with and without asthma.
    Journal of Allergy and Clinical Immunology 09/2014; · 12.05 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. In the present study, we investigated the effect of prophylactic treatment with the intact and F(ab’)2 forms of an anti-G protein monoclonal antibody (mAb), 131-2G, on the humoral and cellular adaptive immune response to RSV rA2-line19F (r19F) challenge in BALB/c mice. The F(ab’)2 form of 131-2G does not decrease virus replication but intact 131-2G does. The serum specimens for antibodies and spleen cells for memory T cell responses to RSV antigens were analyzed at 30, 45, 75 and 95 p.i. with/without prior treatment with 131-2G. The ratios of Th2/Th1 antibody isotypes at each time p.i indicated that both forms of mAb 131-2G shifted the subclass response from a Th2 (IgG1 and IgG2b) to a Th1 (IgG2A) bias. The ratio of IgG1/IgG2A antibody titer was 3-fold to 10-fold higher for untreated than mAb treated mice. There was also some increase in IgG (22%±13 increase) and neutralization (32% increase) in antibodies with mAb 131-2G prophylaxis at 75 days p.i. Treatment with 131-2G significantly (p≤0.001) decreased the percent of IL-4 positive CD4 and CD8 in RSV stimulated spleen cells at all times p.i. while percent of IFN-γ T cells significantly (p≤0.001) increased ≥75 days p.i. The shift from a Th2 to a Th1 biased T cell response in treated compared to untreated mice likely was directed by the much higher levels of T-box transcription factor (Tbet) (≥45% vs <10%) in CD4 and CD8 T cells and lower levels of Gata-3 (≤2% vs ≥6%) in CD4 T cells in peptide stimulated, day 75 p.i. spleen cells. These data show that the RSV G protein affects both humoral and cellular adaptive immune responses and induction of 131-2G-like antibodies might improve the safety and long term efficacy of an RSV vaccine.
    Journal of Virology 08/2014; · 5.08 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) is a leading pediatric pathogen that is responsible for a majority of infant hospitalizations due to viral disease. Despite its clinical importance, no vaccine prophylaxis against RSV disease or effective antiviral therapeutic is available. In this study, we established a robust high-throughput drug screening protocol by using a recombinant RSV reporter virus to expand the pool of RSV inhibitor candidates. Mechanistic characterization revealed that a potent newly identified inhibitor class blocks viral entry through specific targeting of the RSV fusion (F) protein. Resistance against this class was induced and revealed overlapping hotspots with diverse, previously identified RSV entry blockers at different stages of preclinical and clinical development. A structural and biochemical assessment of the mechanism of unique, broad RSV cross-resistance against structurally distinct entry inhibitors demonstrated that individual escape hotspots are located in immediate physical proximity in the metastable conformation of RSV F and that the resistance mutations lower the barrier for prefusion F triggering, resulting in an accelerated RSV entry kinetics. One resistant RSV recombinant remained fully pathogenic in a mouse model of RSV infection. By identifying molecular determinants governing the RSV entry machinery, this study spotlights a molecular mechanism of broad RSV resistance against entry inhibition that may affect the impact of diverse viral entry inhibitors presently considered for clinical use and outlines a proactive design for future RSV drug discovery campaigns.
    Proceedings of the National Academy of Sciences of the United States of America. 08/2014;
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    ABSTRACT: Immune-mediated lung injury is a hallmark of RSV lower respiratory tract illness. STAT4 plays a critical role in CD4+ Th1 lineage differentiation and IFN-γ protein expression by CD4+ T cells. As CD4+ Th1 differentiation is associated with negative regulation of CD4+ Th2 and Th17 differentiation, we hypothesized that RSV infection of STAT4(-/-) mice would result in enhanced lung Th2 and Th17 inflammation and impaired lung Th1 inflammation compared to WT mice. We performed primary and secondary RSV challenge in WT and STAT4(-/-) mice, and used STAT1(-/-) mice as a primary challenge positive control for the development of RSV-specific lung Th2 and Th17 inflammation. Primary RSV challenge of STAT4(-/-) mice resulted in decreased T-bet and IFN-γ expression in CD4+ T cells compared to WT mice. Lung Th2 and Th17 inflammation did not develop in primary RSV-challenged STAT4(-/-) mice. Decreased IFN-γ expression by NK cells, CD4+ T cells, and CD8+ T cells was associated with attenuated weight loss and enhanced viral clearance with primary challenge in STAT4(-/-) mice compared to WT mice. Following secondary challenge, WT and STAT4(-/-) mice also did not develop lung Th2 or Th17 inflammation. In contrast to primary challenge, secondary RSV challenge of STAT4(-/-) mice resulted in enhanced weight loss, increased lung IFN-γ expression, and an increased lung RSV-specific CD8+ T cell response compared to WT mice. These data demonstrate that STAT4 regulates the RSV-specific CD8+ T cell response to secondary infection, but does not independently regulate lung Th2 or Th17 immune responses to RSV challenge.
    Journal of virology. 06/2014;
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    ABSTRACT: The Th17 cytokines IL-17A, IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens including Klebsiella pneumoniae (KP). Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with KP. We hypothesized that pre-existing allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute KP infection and thereby increases lung KP burden. As hypothesized, we found that allergic airway inflammation decreased KP-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in post-infection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased lung KP burden and post-infection mortality. We showed that decreased lung KP burden was independent of IL-4, IL-5, and IL-17A, and partially-dependent on IL-13 and STAT6. Additionally, we demonstrated that decreased lung KP burden associated with allergic airway inflammation was both neutrophil and CCL8-dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against KP and suggest new methods of orchestrating lung antibacterial immunity.
    Infection and immunity 06/2014; · 4.21 Impact Factor
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    PLoS Pathogens 04/2014; 10(4):e1004016. · 8.14 Impact Factor
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    ABSTRACT: Maternal immunization of mice with formalin inactivated respiratory syncytial virus (FI-RSV) resulted in the passive transfer of RSV antibodies but not cellular components to the offspring. The offspring born to FI-RSV immunized mothers showed serum RSV neutralizing activity, effectively controlled lung viral loads without vaccine-enhanced disease, did not induce pulmonary eosinophilia, and cytokine producing cells after live RSV infection. Therefore, this study provides evidence that maternal immunization provides an in vivo model in investigating the roles of antibodies independent of cellular components.
    Antiviral research 01/2014; · 3.61 Impact Factor
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    Christopher C Stobart, Martin L Moore
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    ABSTRACT: RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.
    Viruses. 01/2014; 6(7):2531-50.
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    ABSTRACT: Background The prevalence of allergic diseases has doubled in developed countries in the past several decades. Cyclooxygenase (COX)-inhibiting drugs augmented allergic diseases in mice by increasing allergic sensitization and memory immune responses. However, whether COX inhibition can promote allergic airway diseases by inhibiting immune tolerance is not known. Objective To determine the role of the COX pathway and prostaglandin I2 (PGI2) signaling through the PGI2 receptor (IP) in aeroallergen-induced immune tolerance. Methods Wild-type (WT) BALB/c mice and IP knockout mice were aerosolized with ovalbumin (OVA) to induce immune tolerance prior to immune sensitization with an intraperitoneal injection of OVA/alum. The COX inhibitor indomethacin or vehicle was administered in drinking water to inhibit enzyme activity during the sensitization phase. Two weeks after sensitization, the mice were challenged with OVA aerosols. Mouse bronchoalveolar lavage fluid was harvested for cell counts and TH2 cytokine measurements. Results WT mice treated with indomethacin had greater numbers of total cells, eosinophils, and lymphocytes, and increased IL-5 and IL-13 protein expression in BAL fluid compared to vehicle-treated mice. Similarly, IP knockout mice had augmented inflammation and TH2 cytokine responses compared to WT mice. In contrast, the PGI2 analog cicaprost attenuated the anti-tolerance effect of COX inhibition. Conclusion COX inhibition abrogated immune tolerance by suppressing PGI2 IP signaling, suggesting that PGI2 signaling promotes immune tolerance and that clinical use of COX-inhibiting drugs may increase the risk of developing allergic diseases.
    Journal of Allergy and Clinical Immunology. 01/2014;
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    Jia Meng, Sujin Lee, Anne L Hotard, Martin L Moore
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    ABSTRACT: Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in children for which there is no licensed vaccine. Live-attenuated RSV vaccines are the most clinically advanced in children, but achieving an optimal balance of attenuation and immunogenicity is challenging. One way to potentially retain or enhance immunogenicity of attenuated virus is to mutate virulence genes that suppress host immune responses. The NS1 and NS2 virulence genes of the RSV A2 strain were codon deoptimized according to either human or virus codon usage bias, and the resulting recombinant viruses (dNSh and dNSv, respectively) were rescued by reverse genetics. RSV dNSh exhibited the desired phenotype of reduced NS1 and NS2 expression. RSV dNSh was attenuated in BEAS-2B and primary differentiated airway epithelial cells but not in HEp-2 or Vero cells. In BALB/c mice, RSV dNSh exhibited a lower viral load than did A2, and yet it induced slightly higher levels of RSV-neutralizing antibodies than did A2. RSV A2 and RSV dNSh induced equivalent protection against challenge strains A/1997/12-35 and A2-line19F. RSV dNSh caused less STAT2 degradation and less NF-κB activation than did A2 in vitro. Serial passage of RSV dNSh in BEAS-2B cells did not result in mutations in the deoptimized sequences. Taken together, RSV dNSh was moderately attenuated, more immunogenic, and equally protective compared to wild-type RSV and genetically stable.
    mBio 01/2014; 5(5). · 6.88 Impact Factor
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    ABSTRACT: Immunization of mice with a mixed vaccine (FdFG VLP) of virus-like nanoparticles (VLPs) containing respiratory syncytial virus (RSV) F and G glycoproteins and plasmid DNA encoding RSV F induced IgG2a antibodies dominantly specific for RSV F. After RSV challenge, FdFG VLP immunized mice controlled lung viral loads as well as showed higher levels of CD8 + T cells producing interferon-gamma and did not cause eosinophilia and pulmonary inflammatory disease compared to formalin-inactivated RSV immunized mice.
    Nanomedicine: Nanotechnology, Biology and Medicine. 01/2014;
  • Martin L Moore, Kate L Stokes, Tina V Hartert
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    ABSTRACT: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRI) and viral death in infants. RSV disease in infants is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia and obstructive pulmonary mucus. Human rhinoviruses (HRVs) are by far the most common cause of symptomatic upper respiratory tract infection (URI) in people and are more recently appreciated as a significant cause of LRI. RSV and HRV are also implicated in asthma pathogenesis. Within both RSV and HRV, viral genetic differences play a role in disease severity and/or prevalence in patient populations, and viral genetic differences affect pathogenesis. Here, we review data on how viral genetic differences impact disease using RSV and HRV as examples, including effects on the host immune response. Virus genotype–phenotype relationships can be exploited in the laboratory to gain insight into mechanisms by which respiratory viruses modulate host immune responses and cause disease.
    Current opinion in immunology 12/2013; 25(6):761-8. · 10.88 Impact Factor
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    Sujin Lee, Robert S Mittler, Martin L Moore
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    ABSTRACT: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. No vaccines for RSV are in use. Because of immunosenescence, the immunologic requirements for a successful RSV vaccine in the elderly might differ from a RSV vaccine for young children. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired Ag-specific CD8(+) T cell responses and delayed RSV clearance compared with young mice. To study vaccine-elicited RSV-specific CD8(+) T cells in aged mice, we used a peptide vaccine approach. TriVax is a commixture of a peptide representing immunodominant RSV CD8(+) T cell epitope M282-90, a TLR agonist (polyinosinic-polycytidylic acid), and a costimulatory anti-CD40 Ab. TriVax vaccination generated robust, polyfunctional, and protective CD8(+) T cell responses in young BALB/c mice, but not in 18-mo-old (aged) BALB/c mice. We hypothesized that treatment of aged mice with agonistic anti-CD137 (41BB) mAb will partially restore T cell responses and TriVax efficacy in aged mice. We immunized 18-mo-old BALB/c mice twice with TriVax + anti-41BB mAb or TriVax + isotype control Ab. Coadministration of anti-41BB mAb with TriVax enhanced RSV-specific CD8(+) T cell responses and TriVax efficacy in challenge experiments. Triggering the 41BB costimulatory pathway may be a strategy for enhancing T cell responses to vaccines in the elderly.
    The Journal of Immunology 11/2013; · 5.52 Impact Factor
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    ABSTRACT: Confronted with an increasing number of emerging and re-emerging viral pathogens, the identification of novel pathogen-specific and broad-spectrum antivirals has become a major developmental objective. Targeting host factors required for virus replication presents a tangible approach towards novel hits with broadened indication range. However, the identification of developable host-directed antiviral candidates remains challenging. We describe a novel screening protocol that interrogates the myxovirus host-pathogen interactome for broad-spectrum drug candidates and simultaneously probes for conventional, pathogen-directed hits. With resource-efficiency and pan-myxovirus activity as the central developmental parameters, we explored co-screening against two distinct, independently traceable myxoviruses in a single-well setting. Having identified a pair of unrelated pathogenic myxoviruses (influenza A virus and measles virus) with comparable replication kinetics, we observed unimpaired co-replication of both viruses, generated suitable firefly and renilla luciferase reporter constructs, respectively, and validated the protocol up to 384-well plate format. Combined with an independent counterscreen using a recombinant respiratory syncytial virus luciferase reporter, implementation of the protocol identified candidates with broadened anti-myxovirus profile in addition to pathogen-specific hits. Mechanistic characterization revealed a newly discovered broad-spectrum lead that does not block viral entry, but stimulates effector pathways of the innate cellular antiviral response. In summary, we provide proof-of-concept for the efficient discovery of broad-spectrum myxovirus inhibitors in parallel to para- and orthomyxovirus-specific hit candidates in a single screening campaign. The newly identified compound provides a basis for the development of a novel broad-spectrum small-molecule antiviral class.
    Journal of Virology 08/2013; · 5.08 Impact Factor
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    ABSTRACT: The human respiratory syncytial virus (HRSV) fusion (F) protein cytoplasmic tail (CT) and matrix (M) protein are key mediators of viral assembly but the underlying mechanisms are poorly understood. A complementation assay was developed to systematically examine the role of the F protein CT in infectious virus production. The ability of F mutants with alanine substitutions in the CT to complement an Fnull virus in generating infectious progeny was quantitated by flow cytometry. Two CT regions with impact on infectious progeny production were identified: residues 557-566 (CT-R1) and 569-572 (CT-R2). Substitutions in CT-R1 decreased infectivity by 40-85% and increased the level of F-induced cell-cell fusion, but had little impact on assembly of viral surface filaments, which are believed to be virions. Substitutions in CT-R2, as well as deletion of the entire CT, abrogated infectious progeny production and impaired viral filament formation. However, CT-R2 mutations did not block but rather delayed the formation of viral filaments, which continued to form at a low rate and contained the viral M and nucleoprotein (N). Microscopy analysis revealed that substitutions in CT-R2, but not CT-R1, led to accumulation of M and F proteins within and at the perimeter of viral inclusion bodies (IB) respectively. The accumulation of M and F at IBs and coincident strong decrease in filament formation and infectivity upon CT-R2 mutations suggest that F interaction with IBs is an important step in the virion assembly process and that CT residues 569-572 act to facilitate release of M-ribonucleoprotein complexes from IBs.
    Journal of Virology 07/2013; · 5.08 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Increased airway resistance and increased airway mucin production are two manifestations of RSV infection in children. RSV rA2-line19F infection induces pulmonary mucous production and increased breathing effort in BALB/c mice and provides a way to assess these manifestations of RSV disease in an animal model. In the present study, we investigated the effect of prophylactic treatment with the F(ab')2 form of the anti-G protein monoclonal antibody (mAb), 131-2G, on disease in RSV rA2-line19F challenged mice. F(ab')2 131-2G does not affect virus replication. It, and the intact form that does decrease virus replication, prevented increased breathing effort and airway mucin production, as well as weight loss, pulmonary inflammatory cell infiltration, pulmonary substance P levels, and pulmonary Th2 cytokine levels that occur in mice challenged with this virus. These data suggest that the RSV G protein contributes to prominent manifestations of RSV disease, and mAb 131-2G can prevent these manifestations of RSV disease without inhibiting virus infection.
    Journal of Virology 07/2013; · 5.08 Impact Factor
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    ABSTRACT: Respiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. It has been shown that infection of BALB/cJ mice with RSV clinical isolate A2001/2-20 (2-20) results in greater early viral load and airway necrosis, IL-13 levels, and airway mucin expression than infection with RSV laboratory strain A2. We hypothesized that the fusion (F) protein of RSV 2-20 is a mucus-inducing viral factor. In vitro, the fusion activity of 2-20 F, but not A2 F, was enhanced by expression of RSV G. We generated a recombinant F-chimeric RSV by replacing the F gene of A2 with the F gene of 2-20. Similar to the parent 2-20 strain, infection of BALB/cJ mice with A2-2-20F resulted in greater early viral load and subsequent pulmonary mucin expression than the A2 strain. A2-2-20F infection induced greater necrotic airway damage and neutrophil infiltration than A2 infection. We hypothesized that the neutrophil response to A2-2-20F infection is involved in mucin expression. Antibody-mediated depletion of neutrophils in RSV-infected mice resulted in lower TNF-α levels, fewer IL-13-expressing CD4 T cells, and less airway mucin production in the lung. Our data are consistent with a model in which F and G functional interaction leads to enhanced fusion, and F is a key factor in airway epithelium infection, pathogenesis, and subsequent airway mucin expression.
    Journal of Virology 07/2013; · 5.08 Impact Factor

Publication Stats

406 Citations
220.92 Total Impact Points

Institutions

  • 2014
    • Children's Healthcare of Atlanta
      Atlanta, Georgia, United States
  • 2009–2014
    • Emory University
      • Department of Pediatrics
      Atlanta, Georgia, United States
  • 2013
    • University of Atlanta
      Atlanta, Georgia, United States
  • 2006–2009
    • Vanderbilt University
      • • Department of Pediatrics
      • • Department of Medicine
      Nashville, MI, United States
    • University of Michigan
      • Department of Pathology
      Ann Arbor, MI, United States