PROJECT 1: RSV bronchiolitis and early childhood asthma are the most common, serious, acute, and chronic conditions of infancy and childhood, respectively, and diseases that disproportionately burden vulnerable populations. Opportunity and Impact. This project draws together three important elements in understanding the role of RSV on recurrent wheezing and asthma inception - RSV infection severity, host response and susceptibility. In studying the association of RSV with asthma inception, studies have overwhelmingly focused on the 3-5% of RSV-infected infants requiring hospitalization, while the vast majority of RSV infections are mild. Whether mild infection confers intermediate risk or has a protective effect is an important question. The answer will influence proposals for primary asthma prevention strategies. The proposed series of investigations will aid in our understanding of the role and mechanisms through which RSV may both lead to chronic lung disease, and may protect from chronic lung disease. Approach. Utilizing the ReSPIRA cohort, established for this investigation and described in Core B, we will investigate the relationship between infant RSV infection, host response to infection, and genetic determinants of recurrent wheezing, asthma and allergic disease development following RSV infection.
Our specific aims are to: (1) Establish the association between RSV LRTI, RSV URI/exposure, and no RSV infection in the first 6 months of life on the risk of recurrent wheezing and asthma, (2) Define whether host immune response and/or airway injury biomarkers assessed during infant RSV infection are associated with recurrent wheezing, atopic disease or early childhood asthma, and (3) Identify the genetic determinants of the phenotype of recurrent wheezing, early childhood asthma and atopy following infant RSV infection. Utilizing the ReSPIRA cohort which includes 2000 infants followed from early infancy through early childhood, and established through this U19 grant, this project will answer the following questions: (1) how does RSV cause asthma, (2) does mild RSV infection during infancy increase or decrease the risk of asthma, and (3) what host factors are important in the progression from infant RSV infection to early childhood asthma. Answering these questions will allow us to develop preventive interventions for chronic lung disease in children, and ultimately improve the health of infants and children with bronchiolitis and asthma in the U.S. and worldwide.
Respiratory syncytial virus (RSV) and asthma are the major causes of infant and early childhood morbidity, respectively. Severe RSV infection has also been linked to subsequent asthma development. This project will answer the following questions: (1) how does RSV cause asthma, (2) does mild RSV infection during infancy increase or decrease the risk of asthma, and (3) which host, environmental and genetic factors are important in the progression from infant RSV infection to early childhood asthma. Answering these questions will allow us to develop preventive interventions for chronic lung disease in children.
|Lee, Yu-Na; Hwang, Hye Suk; Kim, Min-Chul et al. (2015) Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease. Antiviral Res 115:8-Jan|
|Ko, Eun-Ju; Kwon, Young-Man; Lee, Jong Seok et al. (2015) Virus-like nanoparticle and DNA vaccination confers protection against respiratory syncytial virus by modulating innate and adaptive immune cells. Nanomedicine 11:99-108|
|Kwon, Young-Man; Hwang, Hye Suk; Lee, Jong Seok et al. (2014) Maternal antibodies by passive immunization with formalin inactivated respiratory syncytial virus confer protection without vaccine-enhanced disease. Antiviral Res 104:1-6|
|Lee, Sujin; Quan, Fu-Shi; Kwon, Youngman et al. (2014) Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins. Antiviral Res 111:129-35|
|Meng, Jia; Lee, Sujin; Hotard, Anne L et al. (2014) Refining the balance of attenuation and immunogenicity of respiratory syncytial virus by targeted codon deoptimization of virulence genes. MBio 5:e01704-14|
|Meng, Jia; Stobart, Christopher C; Hotard, Anne L et al. (2014) An overview of respiratory syncytial virus. PLoS Pathog 10:e1004016|
|Wong, Terianne M; Boyapalle, Sandhya; Sampayo, Viviana et al. (2014) Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology. PLoS One 9:e88764|
|Dulek, Daniel E; Newcomb, Dawn C; Toki, Shinji et al. (2014) STAT4 deficiency fails to induce lung Th2 or Th17 immunity following primary or secondary respiratory syncytial virus (RSV) challenge but enhances the lung RSV-specific CD8+ T cell immune response to secondary challenge. J Virol 88:9655-72|
|Zhou, Weisong; Goleniewska, Kasia; Zhang, Jian et al. (2014) Cyclooxygenase inhibition abrogates aeroallergen-induced immune tolerance by suppressing prostaglandin I2 receptor signaling. J Allergy Clin Immunol 134:698-705.e5|
|Yan, Dan; Lee, Sujin; Thakkar, Vidhi D et al. (2014) Cross-resistance mechanism of respiratory syncytial virus against structurally diverse entry inhibitors. Proc Natl Acad Sci U S A 111:E3441-9|
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