Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Pappas, Claudia; Aguilar, Patricia V.; Basler, Christopher F.; Solórzano, Alicia; Zeng, Hui; Perrone, Lucy A.; Palese, Peter; Garcı́a-Sastre, Adolfo; Katz, Jacqueline M.; Tumpey, Terrence M.

doi:10.1073/pnas.0711815105

Cited by 144 publications

(151 citation statements)

References 36 publications

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“…The influenza virus M1, NS1, and NA proteins have been reported to be related to apoptosis induction [13,16,30]. Also the importance of HA in apoptotic cell death in vitro is further supported by recent findings showing that the HA of the 1918 pandemic influenza virus enhances mortality in mice [11,18,26].…”

Section: Discussionmentioning

confidence: 92%

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

et al. 2010

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The influenza virus generally causes damage to epithelial cells of respiratory tract and infection of cells with this virus often results in cell death with apoptotic characteristics. Reports are available implicating influenza virus as a causative agent of chromosomal aberrations in cells and culture. The objective of this study was to analyze the process of cell death caused by influenza virus (A/Udorn/317/72, H3N2) infection in cultured HeLa cells by electron microscopy and comet assay. The apoptotic study was performed using light microscopy electron microscopy and comet assay to observe the changes in cell morphology and DNA fragmentation. HeLa cells, infected with influenza virus were harvested at various time periods to observe the ultrastructural changes. This infection gave rise to nuclear fragmentation and chromatin condensation accompanied by chromosomal DNA fragmentation into oligonucleosomes. The pattern of comet assay revealed that the apoptosis occurred due to fragmentation of the DNA of the cells which reached the maximum level at 36 h post infection. Ultrastructural study showed extensive chromatin condensation and nuclear fragmentation which are the characteristic features of apoptosis.

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Section: Discussionmentioning

confidence: 92%

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

et al. 2010

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“…Previous studies have shown that influenza uses sialic acid on epithelial cells to cleave hemagglutinin and infect the cells (19). Perhaps individuals with asthma have increased protease activation leading to increased susceptibility to infection.…”

Section: Discussionmentioning

confidence: 99%

Increased H1N1 Infection Rate in Children with Asthma

Kloepfer¹,

Olenec²,

Lee³

et al. 2012

Am J Respir Crit Care Med

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Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009-2010 flu season. Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma. Methods: One hundred and eighty children, 4-12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples. Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8-9; P , 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9-7.2; P ¼ 0.07). Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.Keywords: asthma; viral infection; influenza 2009 H1N1 Flu was first reported in the United States in the spring of 2009, and eventually affected 61 million people (1), one-third of them children. Morbidity was high, with 87,000 children requiring hospitalization. The most common comorbidity for patients hospitalized as a result of H1N1 infection was asthma (2), and the percentage of children with asthma hospitalized because of the 2009 H1N1 virus was two-to fivefold higher than previous reports of hospitalization due to seasonal influenza (3, 4). Despite the observation that subjects with asthma suffer H1N1 illness with increased severity, it remains unclear at what rate they are infected and whether their symptom severity is greater than those of their nonasthmatic counterparts. Previous studies of H1N1 infectivity reflect symptomatic infections with limited reporting of mild or asymptomatic infection (5-7).A study by our group demonstrated that 90% of children with asthma are infected with human rhinoviruses (HRVs) during the month of September, and that the severity of clinical illness varies from no symptoms to severe wheezing illnesses (8). This study provided the foundation on which we designed a larger cohort to prospectively examine the relationship between illness symptom...

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“…Among the most important factors regulating sites of viral replication, levels of viral replication, and viral pathogenesis for type A influenza viruses in mammals are viral HA sequence, host cell receptor type, viral polymerases (PB1, PB2, PA), viral neuraminidase, and viral nonstructural proteins (NS1). 1,22 Viral HA binds to host receptors with oligosaccharides ending in sialic-acid a-2,6-galactose (SAa-2,6gal) or sialic-acid a-2,3-galactose (SAa-2,3gal). There are species and topographical cell differences in density of SAa-2,6gal and SAa-2,3gal cell receptors in the respiratory tract.…”

Section: Discussionmentioning

confidence: 99%

“…BALB/c mice were chosen because they are widely used in influenza A virus pathogenesis studies. 5,13,22 Mice were weighed and monitored daily. Mice were euthanatized by anesthesia with urethane and exsanguination and by pneumothorax before tissue collection.…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

Canine H3N8 Influenza Virus Infection in Dogs and Mice

Castleman

Crawford

et al. 2010

Vet Pathol

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An H3N8 influenza virus closely related to equine influenza virus was identified in racing greyhound dogs with respiratory disease in 2004 and subsequently identified in shelter and pet dogs. Pathologic findings in dogs spontaneously infected with canine influenza virus were compared with lesions induced in beagle and mongrel dogs following experimental inoculation with influenza A/canine/Florida/43/2004. BALB/c mice were inoculated with canine influenza virus to assess their suitability as an experimental model for viral pathogenesis studies. All dogs inoculated with virus developed necrotizing and hyperplastic tracheitis and bronchitis with involvement of submucosal glands as well as mild bronchiolitis and pneumonia. Viral antigen was identified in bronchial and tracheal epithelial cells of all dogs and in alveolar macrophages of several dogs. Many dogs that were spontaneously infected with virus also developed bacterial pneumonia, and greyhound dogs with fatal spontaneous infection developed severe pulmonary hemorrhage with hemothorax. Virus-inoculated BALB/c mice developed tracheitis, bronchitis, bronchiolitis, and mild pneumonia in association with viral antigen in airway epithelial cells and in type 2 alveolar epithelial cells. Virus was not detected in extrarespiratory sites in any animals. The results indicate that canine influenza virus infection consistently induces acute tracheitis and bronchitis in dogs. Mice may be a useful model for some pathogenesis studies on canine influenza virus infection.

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Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus

Cited by 144 publications

References 36 publications

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

Increased H1N1 Infection Rate in Children with Asthma

Canine H3N8 Influenza Virus Infection in Dogs and Mice

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