IntroductionInherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains.MethodsWe studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection.ResultsMultivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A0 were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A1 was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A1 haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A0 (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A1 was associated with a higher PaO2/FiO2 ratio (P = 0.001).ConclusionsOur data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A1) SP-A2 for future IAV pandemics.
Influenza virus infection (IVI) is typically subclinical or causes a self-limiting upper respiratory disease. However, in a small subset of patients IVI rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a minority of patients require intensive care unit admission. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IVI. However, the molecular basis of such human factors remains largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is associated with a population-attributable risk of 5.4 % for severe IVI in Northern Europeans and 54.3 % for severe H1N1pdm infection in Chinese. A total of 148 patients with confirmed IVI were considered for recruitment; 118 Spanish patients (60 of them hospitalized with PVP) and 246 healthy Spanish individuals were finally included in the statistical analysis. PCR-RFLP was used with confirmation by Sanger sequencing. The allele frequency for rs12252-C was found to be 3.5 % among the general Spanish population. We found no rs12252-C homozygous individuals in our control group. The only Spanish patient homozygous for rs12252-C had a neurological disorder (a known risk factor for severe IVI) and mild influenza. Our data do not suggest a role of rs12252-C in the development of severe IVI in our population. These data may be relevant to recognize whether patients homozygous for rs12252-C are at risk of severe influenza, and hence require individualized measures in the case of IVI.
The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.
López-Rodríguez , M. A., P. Chiu-Alvarado y J. C, Rojas. 2009. Factores que afectan la atracción deProrops nasuta Waterston (Hymenoptera: Bathylidae) a los olores emitidos por los desechos de su huésped, la broca del café. Acta Zool. Mex (n. s.) 25(1): 49-60. RESUMEN. Prorops nasuta Waterston (Hymenoptera: Bathylidae) es un ectoparásito que se alimenta de todos los estados inmaduros de la broca del café, Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scotylinae) y que se reproduce depositando sus huevecillos en la parte ventral de las larvas maduras y pupas de su huésped. Estudios previos han demostrado que este parasitoide es atraído a los olores provenientes de los desechos alimenticios y fecales de su huésped. Este estudio investigó el efecto de algunos factores tales como edad, alimentación, sexo y experiencia de oviposición en la respuesta del parasitoide P. nasuta a los olores provenientes de los desechos de su huésped. Los bioensayos se realizaron en un olfactómetro tipo "Y". Los resultados muestran que las hembras de P. nasuta sin alimentar y alimentadas con miel-agua prefirieron significativamente los olores provenientes de los desechos que al control. En contraste, las hembras alimentadas con inmaduros no mostraron ninguna preferencia por los olores de los desechos o por el control. Los resultados muestran que la edad de las hembras no influyó en su respuesta a los olores de los desechos de su huésped. Los machos de P. nasuta no fueron atraídos a los olores provenientes de los desechos. La previa experiencia de las hembras no influyó en su respuesta a los olores de los desechos. Palabras clave: Control biológico, broca del café, Prorops nasuta, localización del huésped, cairomonas.López-Rodríguez , M. A., P. Chiu-Alvarado & J. C, Rojas. 2009. Factors affecting the attraction of Prorops nasuta Waterston (Hymenoptera: Bathylidae) to odors emitted by dust/frass of its host, the coffee berry borer. Acta Zool. Mex (n. s.) 25(1): 49-60 ABSTRACT. The parasitoid Prorops nasuta Waterston (Hymenoptera: Bathylidae) is a wasp that feeds upon and parasitizes the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), which is the most important pest of coffee (Coffea spp.) in the world. Previous studies have shown that P. nasuta females are attracted to the odors emitted by dust/frass of H. hampei. In this study, the effect of age, feeding status, sex and previous experience of P. nasuta on
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