- Human inborn errors of immunity to infection affecting cells other than leukocytes: from the immune system to the whole organism. [Review]
- COCurr Opin Immunol 2019 May 20; 59:88-100
- Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically esse…
Studies of vertebrate immunity have traditionally focused on professional cells, including circulating and tissue-resident leukocytes. Evidence that non-professional cells are also intrinsically essential (i.e. not via their effect on leukocytes) for protective immunity in natural conditions of infection has emerged from three lines of research in human genetics. First, studies of Mendelian resistance to infection have revealed an essential role of DARC-expressing erythrocytes in protection against Plasmodium vivax infection, and an essential role of FUT2-expressing intestinal epithelial cells for protection against norovirus and rotavirus infections. Second, studies of inborn errors of non-hematopoietic cell-extrinsic immunity have shown that APOL1 and complement cascade components secreted by hepatocytes are essential for protective immunity to trypanosome and pyogenic bacteria, respectively. Third, studies of inborn errors of non-hematopoietic cell-intrinsic immunity have suggested that keratinocytes, pulmonary epithelial cells, and cortical neurons are essential for tissue-specific protective immunity to human papillomaviruses, influenza virus, and herpes simplex virus, respectively. Various other types of genetic resistance or predisposition to infection in human populations are not readily explained by inborn variants of genes operating in leukocytes and may, therefore, involve defects in other cells. The probing of this unchartered territory by human genetics is reshaping immunology, by scaling immunity to infection up from the immune system to the whole organism.
- Potential effect of germanium exposure on the risk of influenza-like illness in housewives in Shanxi Province, China. [Journal Article]
- STSci Total Environ 2019 May 09; 682:208-212
- Few studies have examined the relationship between exposure to germanium (Ge) and the risk of influenza-like illness (ILI). Therefore, we investigated the association of Ge exposure and its interacti…
Few studies have examined the relationship between exposure to germanium (Ge) and the risk of influenza-like illness (ILI). Therefore, we investigated the association of Ge exposure and its interaction with single nucleotide polymorphisms (SNPs) related to Phase II metabolism on ILI risk among housewives in Shanxi Province, northern China. This cross-sectional study enrolled 373 housewives. Information on the housewives' characteristics and the frequency of ILI was collected by questionnaire. We analyzed the Ge concentrations in hair samples taken from near the scalp at the back of the head. Blood samples were used to identify SNPs related to Phase II metabolism. The results suggested that the hair Ge concentration was associated with ILI risk with an adjusted odds ratio and 95% confidence interval of 2.59 (1.61-4.19). A significant dose-response relationship was observed without or with adjusting for confounders. We did not observe any interaction effect between the hair Ge concentration and the SNPs on ILI risk. We found that high dietary consumption of meat and fried foods was positively correlated with the hair Ge concentration. Therefore, chronic Ge exposure may be a risk factor for an increased frequency of ILI in housewives.
- Exploitation of glycosylation in enveloped virus pathobiology. [Review]
- BBBiochim Biophys Acta Gen Subj 2019 May 20
- Glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. As obligate parasites, viruses exploit host-cell machinery to glycosylate their …
Glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. As obligate parasites, viruses exploit host-cell machinery to glycosylate their own proteins during replication. Viral envelope proteins from a variety of human pathogens including HIV-1, influenza virus, Lassa virus, SARS, Zika virus, dengue virus, and Ebola virus have evolved to be extensively glycosylated. These host-cell derived glycans facilitate diverse structural and functional roles during the viral life-cycle, ranging from immune evasion by glycan shielding to enhancement of immune cell infection. In this review, we highlight the imperative and auxiliary roles glycans play, and how specific oligosaccharide structures facilitate these functions during viral pathogenesis. We discuss the growing efforts to exploit viral glycobiology in the development of anti-viral vaccines and therapies.
- A possible European origin of the Spanish influenza and the first attempts to reduce mortality to combat superinfecting bacteria: an opinion from a virologist and a military historian. [Journal Article]
- HVHum Vaccin Immunother 2019 May 23; :1-4
- When we reconsider the virology and history of the Spanish Influenza Pandemic, the science of 2018 provides us with tools which did not exist at the time. Two such tools come to mind. The first lies …
When we reconsider the virology and history of the Spanish Influenza Pandemic, the science of 2018 provides us with tools which did not exist at the time. Two such tools come to mind. The first lies in the field of 'gain of function' experiments. A potential pandemic virus, such as influenza A (H5N1), can be deliberately mutated in the laboratory in order to change its virulence and spreadability. Key mutations can then be identified. A second tool lies in phylogenetics, combined with molecular clock analysis. It shows that the 1918 pandemic virus first emerged in the years 1915-1916. We have revisited the literature published in Europe and the United States, and the notes left by physicians who lived at the time. In this, we have followed the words of the late Alfred Crosby: who wrote that "contemporary documentary evidence from qualified physicians" is the key to understanding where and how the first outbreaks occurred. In our view, the scientists working in Europe fulfill Crosby's requirement for contemporary evidence of origin. Elsewhere, Crosby also suggested that "the physicians of 1918 were participants in the greatest failure of medical science in the twentieth century". Ours is a different approach. We point to individual pathologists in the United States and in France, who strove to construct the first universal vaccines against influenza. Their efforts were not misdirected, because the ultimate cause of death in nearly all cases flowed from superinfections with respiratory bacteria.
- Influenza vaccination in the elderly: 25 years follow-up of a randomized controlled trial. No impact on long-term mortality. [Journal Article]
- PlosPLoS One 2019; 14(5):e0216983
- Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcom…
Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcome of influenza vaccination on mortality in the elderly by conducting a 25-year follow-up study of a RCT on the efficacy of influenza vaccination as baseline. The RCT had been conducted in the Netherlands 5 years before vaccination was recommended for those aged >65 and 17 years before recommending it for those aged >60. The RCT included 1838 community-dwelling elderly aged ≥ 60 that had received an intramuscular injection with the inactivated quadrivalent influenza vaccine (n = 927) or placebo (n = 911) during the 1991/1992 winter. In our follow-up study, outcomes included all-cause mortality, influenza-related mortality and seasonal mortality. Unadjusted and adjusted hazard ratios (HRs) were estimated by Cox regression and sub-hazard ratios (SHRs) by competing risk models. Secondary analyses included subgroup analyses by age and disease status. The vital status up to January 1, 2017 was provided in 1800/1838 (98%) of the cases. Single influenza vaccination did not reduce all-cause mortality when compared to placebo (adjusted HR 0.95, 95% CI 0.85-1.05). Also, no differences between vaccination and placebo group were shown for underlying causes of death or seasonal mortality. In those aged 60-64, median survival increased with 20.1 months (95% CI 2.4-37.9), although no effects on all-cause mortality (adjusted HR 0.86, 95% CI 0.72-1.03) could be demonstrated in survival analysis. In conclusion, this study did not demonstrate a statistically significant effect following single influenza vaccination on long-term mortality in community-dwelling elderly in general. We propose researchers designing future studies on influenza vaccination in the elderly to fit these studies for longer-term follow-up, and suggest age-group comparisons in observational research. Clinical trial registry number: NTR6179.
- Forecasting national and regional influenza-like illness for the USA. [Journal Article]
- PCPLoS Comput Biol 2019 May 23; 15(5):e1007013
- Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our…
Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.
- Preliminary Assessment of the Efficacy of a T-Cell-Based Influenza Vaccine, MVA-NP+M1, in Humans. [Journal Article]
- CIClin Infect Dis 2019 May 23
- Prevalence and Phylogenetics of H9n2 in Backyard and Commercial Poultry in Pakistan. [Journal Article]
- ADAvian Dis 2018; 62(4):416-424
- Surveillance of H9N2 is currently focused on areas central to the commercial poultry industry. This study determined the prevalence of H9N2 virus in commercial and backyard poultry flocks in Punjab P…
Surveillance of H9N2 is currently focused on areas central to the commercial poultry industry. This study determined the prevalence of H9N2 virus in commercial and backyard poultry flocks in Punjab Province, Pakistan. Oral and tracheal swabs were collected from commercial and backyard poultry from January 2015 through June 2016. Antisera against H5, H7, H9, and Newcastle disease viruses were used for virus identification. Molecular confirmation was made by reverse transcription PCR. Avian influenza virus subtypes H5 and H7 were not detected. The H9N2 virus was isolated in 5.7% of 905 tested flocks (5-10 birds/flock). Prevalence in commercial and backyard poultry was 6.7% of 687 flocks and 2.7% of 218 flocks, respectively. Hemagglutinin and neuraminidase-gene-based phylogenetic analysis of commercial and backyard poultry isolates showed 100% homology. Within sublineage B2 of Pakistan, identity among most recent isolates (2015) was 100%, compared to 75%-99% identity with previously isolated viruses (2010-12), indicating continued virus evolution. Most of the previously reported and currently studied viruses were isolated near the Pakistan-India border. Phylogenetic analysis showed that Pakistani and Indian isolates were closely related, indicating that avian influenza virus transmission may occur across this border.
- Environmental Sampling Survey of H5N2 Highly Pathogenic Avian Influenza-Infected Layer Chicken Farms in Minnesota and Iowa. [Journal Article]
- ADAvian Dis 2018; 62(4):373-380
- Respiratory secretions, feces, feathers, and eggs of avian influenza-infected hens provide ample sources of virus which heavily contaminate barn and farm environments during a disease outbreak. Envir…
Respiratory secretions, feces, feathers, and eggs of avian influenza-infected hens provide ample sources of virus which heavily contaminate barn and farm environments during a disease outbreak. Environmental sampling surveys were conducted in the Midwestern United States on affected farms during the 2015 H5N2 highly pathogenic avian influenza (HPAI) outbreak to assess the degree of viral contamination. A total of 930 samples were obtained from various sites inside and outside layer barns housing infected birds and tested with real-time reverse transcriptase PCR. The distribution and load of viral RNA in barns in which most birds were dead at the onset of depopulation efforts (high-mortality barns) were compared with those of barns in which birds were euthanatized before excess mortality occurred (normal-mortality barns). A statistically significant difference was seen between cycle threshold (Ct) values for samples taken of fans, feed troughs, barn floors, barn walls, cages, manure-associated locations, barn doors, egg belts, and the exterior of high-mortality vs. normal-mortality barns. In high-mortality barns, sample sites were found to be the most to least contaminated in the following order: cages, manure-associated locations, barn floors, egg belts, feed troughs, barn doors, barn walls, fans, exterior, and egg processing. Significant changes in Ct values over time following HPAI detection in a barn and depopulation of birds on an infected farm were observed for the manure-associated, barn floor, barn wall, and fan sampling sites. These results show that high mortality in a flock as a result of HPAI will increase contamination of the farm environment. The results also suggest optimal sampling locations for detection of virus; however, the persistence of RNA on highmortality farms may delay the determination that adequate sanitization has been performed for restocking to take place.
New Search Next
- Virucidal Efficacy of a Quaternary Ammonium Compound with Food Additive-Grade Calcium Hydroxide Toward Avian Influenza Virus and Newcastle Disease Virus on Abiotic Carriers. [Journal Article]
- ADAvian Dis 2018; 62(4):355-363
- The virucidal efficacies of a 0.2% food additive-grade calcium hydroxide [FdCa(OH)2] solution, a quaternary ammonium compound (QAC) diluted at 1:500 (QACx500), and their mixture [Mix500; FdCa(OH)2 po…
The virucidal efficacies of a 0.2% food additive-grade calcium hydroxide [FdCa(OH)2] solution, a quaternary ammonium compound (QAC) diluted at 1:500 (QACx500), and their mixture [Mix500; FdCa(OH)2 powder added at a final concentration of 0.2% to QACx500] were investigated as fomites for avian influenza virus (AIV) and Newcastle disease virus (NDV) on abiotic carriers (steel, rubber, and plastic) at two different temperatures (room temperature [RT; 25 ± 2 C] and 2 C). These viruses were seeded on coupons (5 cm×5 cm) of rubber, steel, or plastic with 5% fetal bovine serum. After complete drying, the coupons were covered with the test solutions at RT or 2 C. After fixed incubation periods, viruses were recovered from the coupons and titrated. At RT, Mix500 required a short time (3 min) to inactivate AIV and NDV to effective levels (≥3 log virus reduction) on rubber, steel, and plastic carriers compared with QAC or FdCa(OH)2. At low temperature, QACx500 inactivated AIV on steel and plastic carriers to effective levels within 60 min, whereas Mix500 did so within 10 min. QACx500 and FdCa(OH)2 solutions could inactivate NDV on steel and plastic carriers within 20 and 10 min, respectively, and Mix500 could do so within 3 min. Viruses on the carriers required longer incubation periods for inactivation at 2 C than at 25 C. These results demonstrate desirable synergistic virucidal effects of Mix500 for important poultry viruses on abiotic carriers, while indicating high applicability within poultry farming.