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Item Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis(Elsevier, 2022) Sanders, Don B.; Deschamp, Ashley R.; Hatch, Joseph E.; Slaven, James E.; Gebregziabher, Netsanet; Kemner-van de Corput, Mariette; Tiddens, Harm A. W. M.; Rosenow, Tim; Storch, Gregory A.; Hall, Graham L.; Stick, Stephen M.; Ranganathan, Sarath; Ferkol, Thomas W.; Davis, Stephanie D.; Pediatrics, School of MedicineBackground: Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF. Methods: Infants with CF were enrolled before 4 months of age. Multiplex PCR assays were performed on nasal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent CT imaging at approximately 12 months of age. Associations between Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) CT scores and respiratory viruses and symptoms were assessed with Spearman correlation coefficients. Results: Sixty infants were included for analysis. Human rhinovirus was the most common virus detected, on 28% of tested nasal swabs and in 85% of participants. The median (IQR) extent of lung fields that was healthy based on PRAGMA-CF was 98.7 (0.8)%. There were no associations between PRAGMA-CF and age at first virus, or detection of any virus, including rhinovirus, respiratory syncytial virus, or parainfluenza. The extent of airway wall thickening was associated with ever having wheezed (ρ = 0.31, p = 0.02) and number of encounters with cough (ρ = 0.25, p = 0.0495). Conclusions: Infants with CF had minimal structural lung disease. We did not find an association between respiratory viruses and CT abnormalities. Wheezing and frequency of cough were associated with early structural changes.Item Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis(Elsevier, 2022-11) Sander, Don B.; Deschamp, Ashley R.; Hatch, Joseph E.; Slaven, James E.; Gebregziabher, Netsanet; Kemner-van de Corput, Mariette; Tiddens, Harm A. W. M.; Rosenow, Tim; Storch, Gregory A.; Hall, Graham L.; Stick, Stephen M.; Ranganathan, Sarath; Ferkol, Thomas W.; Davis, Stephanie D.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF. Methods: Infants with CF were enrolled before 4 months of age. Multiplex PCR assays were performed on nasal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent CT imaging at approximately 12 months of age. Associations between Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) CT scores and respiratory viruses and symptoms were assessed with Spearman correlation coefficients. Results: Sixty infants were included for analysis. Human rhinovirus was the most common virus detected, on 28% of tested nasal swabs and in 85% of participants. The median (IQR) extent of lung fields that was healthy based on PRAGMA-CF was 98.7 (0.8)%. There were no associations between PRAGMA-CF and age at first virus, or detection of any virus, including rhinovirus, respiratory syncytial virus, or parainfluenza. The extent of airway wall thickening was associated with ever having wheezed (ρ = 0.31, p = 0.02) and number of encounters with cough (ρ = 0.25, p = 0.0495). Conclusions: Infants with CF had minimal structural lung disease. We did not find an association between respiratory viruses and CT abnormalities. Wheezing and frequency of cough were associated with early structural changes.Item DescribePROT: database of amino acid-level protein structure and function predictions(Oxford University Press, 2021-01-08) Zhao, Bi; Katuwawala, Akila; Oldfield, Christopher J.; Dunker, A. Keith; Faraggi, Eshel; Gsponer, Jörg; Kloczkowski, Andrzej; Malhis, Nawar; Mirdita, Milot; Obradovic, Zoran; Söding, Johannes; Steinegger, Martin; Zhou, Yaoqi; Kurgan, Lukasz; Medicine, School of MedicineWe present DescribePROT, the database of predicted amino acid-level descriptors of structure and function of proteins. DescribePROT delivers a comprehensive collection of 13 complementary descriptors predicted using 10 popular and accurate algorithms for 83 complete proteomes that cover key model organisms. The current version includes 7.8 billion predictions for close to 600 million amino acids in 1.4 million proteins. The descriptors encompass sequence conservation, position specific scoring matrix, secondary structure, solvent accessibility, intrinsic disorder, disordered linkers, signal peptides, MoRFs and interactions with proteins, DNA and RNAs. Users can search DescribePROT by the amino acid sequence and the UniProt accession number and entry name. The pre-computed results are made available instantaneously. The predictions can be accesses via an interactive graphical interface that allows simultaneous analysis of multiple descriptors and can be also downloaded in structured formats at the protein, proteome and whole database scale. The putative annotations included by DescriPROT are useful for a broad range of studies, including: investigations of protein function, applied projects focusing on therapeutics and diseases, and in the development of predictors for other protein sequence descriptors. Future releases will expand the coverage of DescribePROT. DescribePROT can be accessed at http://biomine.cs.vcu.edu/servers/DESCRIBEPROT/.Item Genetic Determinants of Coxsackievirus B3 Pathogenesis(2020-10) Barnard, April L.; Robinson, Christopher M.; Evans-Molina, Carmella; Yu, AndyEnteric viruses are among the most common infectious human viruses worldwide, causing an estimated 10-15 million infections per year in the United States. Among enteric viruses, Coxsackievirus is commonly isolated and can lead to the development of meningitis, encephalitis, pancreatitis, and hepatitis. Furthermore, Coxsackievirus B3 is the primary cause of viral myocarditis and can lead to pleurodynia, with nearly 40,000 symptomatic cases reported in the United States each year. The enteroviral ssRNA genome contains a 5’ untranslated region (5’UTR) which consists of two structural components, the cloverleaf and the internal ribosome entry site (IRES), both shown to be integral to viral success. Additionally, the viral genome encodes four structural VP proteins as well as 11 non-structural proteins. Polymorphisms found within the CVB3 population have been linked to viral virulence. Here, we compare two CVB3 Nancy variants to elucidate the downstream effects observed in response to mutations found in the CVB3 genome. Implementing our novel oral inoculation model, we aimed to determine the impact mutations found in the 5’UTR and VP regions exert on viral pathogenesis. We also aimed to delineate the in vitro effects of the observed mutations. We investigated the role mutations found in the structural regions played in virus host cell attachment, in vitro cell viability, and replication. Our work has further confirmed the relevance and impact of mutations found in the VP region of the CVB3 genome.Item How satellites can help control the spread of diseases such as Zika(The Conversation US, Inc., 2016-02-15) Moreno-Madriñán, Max Jacobo; Epidemiology, Richard M. Fairbanks School of Public HealthItem The interrelationship between the replication and maturation pathways of SV40(1984) Wang, Hwa-TangItem Mechanism of suppression of Banzi virus replication in Aedes albopictus cells(1984) Hommel, Grace AnnItem Viral Infections(Springer, 2017) Relich, Ryan F.; Pathology and Laboratory Medicine, School of MedicineDespite major advances in basic and applied research and the availability of several vaccines, viral diseases still account for a large proportion of the human infectious disease burden. Many viruses cause self-limiting and relatively mild infections, but several, including human immunodeficiency virus and influenza virus, are responsible for millions of deaths every year throughout the world. Several factors contribute to the enormous impact that viruses have on human health. For example, there are very few therapeutic options available for the treatment of viral infections, and many of those that are available possess a limited spectrum of activity or are designed for the treatment of diseases caused by specific viruses (e.g., oseltamivir is intended for the treatment of influenza only). In addition, the rapid evolution of viruses has led to the emergence of drug-resistant strains against which no currently available therapeutics are effective. Coupled with these and other issues are the appearance of never before seen viruses and the emergence of known but previously underappreciated viruses. Since the beginning of the twenty-first century, numerous “new” viruses, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the 2009 pandemic influenza A virus, and Lujo hemorrhagic fever virus, have made their debut and have proved to be formidable threats to human health. Recently, the appearance of Ebola virus (Zaire ebolavirus) in West Africa, a region that has not previously seen an outbreak of this virus, was marked by an epidemic that afflicted nearly 30,000 individuals and killed more than 11,000 of those who were infected. Most recently, the far-reaching and rapid spread of Zika virus, a mosquito-borne virus that was discovered in the 1940s in Uganda, in the Western Hemisphere has invoked considerable public and scientific attention and has given rise to perhaps the largest concerted effort by scientists to rapidly develop a vaccine to halt the transmission of a virus. Each of these points underscores the importance of further research into improved surveillance, diagnosis, treatment, and prevention of viral diseases.