Lack of group X secreted phospholipase A₂ increases survival following pandemic H1N1 influenza infection.
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ABSTRACT:
SUBMITTER: Kelvin AA
PROVIDER: S-EPMC4106042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.
| S-EPMC3256529 | biostudies-other
Project description:BackgroundIn April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.Methods and findingsAnonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n= 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n=100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.ConclusionsAfter the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.
| S-EPMC2828126 | biostudies-literature
Project description:The 1918 influenza A virus caused the most devastating pandemic, killing approximately 50 million people worldwide. Immunization with 1918-like and classical swine H1N1 virus vaccines results in cross-protective antibodies against the 2009 H1N1 pandemic influenza, indicating antigenic similarities among these viruses. In this study, we demonstrate that vaccination with the 2009 pandemic H1N1 vaccine elicits 1918 virus cross-protective antibodies in mice and humans, and that vaccination or passive transfer of human-positive sera reduced morbidity and conferred full protection from lethal challenge with the 1918 virus in mice. The spread of the 2009 H1N1 influenza virus in the population worldwide, in addition to the large number of individuals already vaccinated, suggests that a large proportion of the population now have cross-protective antibodies against the 1918 virus, greatly alleviating concerns and fears regarding the accidental exposure/release of the 1918 virus from the laboratory and the use of the virus as a bioterrorist agent.
| S-EPMC2964451 | biostudies-other
Project description:Background2009 pandemic influenza A/H1N1 (A(H1N1)pdm09) was first detected in the United States in April 2009 and resulted in a global pandemic. We conducted a serologic survey to estimate the cumulative incidence of A(H1N1)pdm09 through the end of 2009 when pandemic activity had waned in the United States.MethodsWe conducted a pair of cross sectional serologic surveys before and after the spring/fall waves of the pandemic for evidence of seropositivity (titer ?40) using the hemagglutination inhibition (HI) assay. We tested a baseline sample of 1,142 serum specimens from the 2007-2008 National Health and Nutrition Examination Survey (NHANES), and 2,759 serum specimens submitted for routine screening to clinical diagnostic laboratories from ten representative sites.ResultsThe age-adjusted prevalence of seropositivity to A(H1N1)pdm09 by year-end 2009 was 36.9% (95%CI: 31.7-42.2%). After adjusting for baseline cross-reactive antibody, pandemic vaccination coverage and the sensitivity/specificity of the HI assay, we estimate that 20.2% (95%CI: 10.1-28.3%) of the population was infected with A(H1N1)pdm09 by December 2009, including 53.3% (95%CI: 39.0-67.1%) of children aged 5-17 years.ConclusionsBy December 2009, approximately one-fifth of the US population, or 61.9 million persons, may have been infected with A(H1N1)pdm09, including around half of school-aged children.
| S-EPMC3485186 | biostudies-literature
Project description:BackgroundAlterations in lipid metabolism are inherent to the metabolic transformations that support tumorigenesis. The relationship between the synthesis, storage and use of lipids and their importance in cancer is poorly understood. The human group X secreted phospholipase A2 (hGX sPLA2) releases fatty acids (FAs) from cell membranes and lipoproteins, but its involvement in the regulation of cellular FA metabolism and cancer is not known.ResultsHere we demonstrate that hGX sPLA2 induces lipid droplet (LD) formation in invasive breast cancer cells, stimulates their proliferation and prevents their death on serum deprivation. The effects of hGX sPLA2 are shown to be dependent on its enzymatic activity, are mimicked by oleic acid and include activation of protein kinase B/Akt, a cell survival signaling kinase. The hGX sPLA2-stimulated LD biogenesis is accompanied by AMP-activated protein kinase (AMPK) activation, up-regulation of FA oxidation enzymes and the LD-coating protein perilipin 2, and suppression of lipogenic gene expression. Prolonged activation of AMPK inhibited hGX sPLA2-induced LD formation, while etomoxir, an inhibitor of FA oxidation, abrogated both LD formation and cell survival. The hGX sPLA2-induced changes in lipid metabolism provide a minimal immediate proliferative advantage during growth under optimal conditions, but they confer to the breast cancer cells a sustained ability to resist apoptosis during nutrient and growth factor limitation.ConclusionOur results identify hGX sPLA2 as a novel modulator of lipid metabolism that promotes breast cancer cell growth and survival by stimulating LD formation and FA oxidation.
| S-EPMC3852912 | biostudies-literature
Project description:BACKGROUND:Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. METHODS:We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. RESULTS:Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). CONCLUSIONS:Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.
| S-EPMC6708558 | biostudies-literature
Project description:In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents.Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n = 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n = 100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%.After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children.
| S-EPMC2904390 | biostudies-literature
Project description:Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.
| S-EPMC3034774 | biostudies-other
Project description:The emergence of the pandemic 2009 H1N1 influenza A virus in humans and subsequent discovery that it was of swine influenza virus lineages raised concern over the safety of pork. Pigs experimentally infected with pandemic 2009 H1N1 influenza A virus developed respiratory disease; however, there was no evidence for systemic disease to suggest that pork from pigs infected with H1N1 influenza would contain infectious virus. These findings support the WHO recommendation that pork harvested from pandemic influenza A H1N1 infected swine is safe to consume when following standard meat hygiene practices.
| S-EPMC2791228 | biostudies-other
Project description:Obese individuals are at greater risk for hospitalization and death from infection with the 2009 pandemic H1N1 influenza virus (pH1N1). In this study, diet-induced and genetic-induced obese mouse models were used to uncover potential mechanisms by which obesity increases pH1N1 severity. High-fat diet-induced and genetic-induced obese mice exhibited greater pH1N1 mortality, lung inflammatory responses, and excess lung damage despite similar levels of viral burden compared with lean control mice. Furthermore, obese mice had fewer bronchoalveolar macrophages and regulatory T cells during infection. Obesity is inherently a metabolic disease, and metabolic profiling has found widespread usage in metabolic and infectious disease models for identifying biomarkers and enhancing understanding of complex mechanisms of disease. To further characterize the consequences of obesity on pH1N1 infection responses, we performed global liquid chromatography-mass spectrometry metabolic profiling of lung tissue and urine. A number of metabolites were perturbed by obesity both prior to and during infection. Uncovered metabolic signatures were used to identify changes in metabolic pathways that were differentially altered in the lungs of obese mice such as fatty acid, phospholipid, and nucleotide metabolism. Taken together, obesity induces distinct alterations in the lung metabolome, perhaps contributing to aberrant pH1N1 immune responses.
| S-EPMC4417391 | biostudies-literature