Specific serology for emerging human coronaviruses by protein microarray

We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV

Interferon (IFN)-γ-Inducible Protein-10: Association with Histological Results, Viral Kinetics, and Outcome during Treatment with Pegylated IFN-α2a and Ribavirin for Chronic Hepatitis C Virus Infection

BackgroundWe investigated associations between interferon (IFN)-γ-inducible protein (IP)-10 and liver histological results, viral kinetic response, and treatment outcome in patients infected with hepatitis C virus (HCV) genotypes 1-4 MethodsPlasma IP-10 was monitored before, during, and after treatment with pegylated IFN-α2a and ribavirin in 265 HCV-infected patients ResultsIn univariate analyses, a low baseline IP-10 level was significantly associated with low baseline viral load, rapid viral response (RVR), a sustained viral response (SVR), body mass index <25 kg/m2, and less-pronounced fibrosis, inflammation, and steatosis (for HCV genotypes other than 3). When the results of the univariate analyses were included in multivariate analyses, a low plasma IP-10 level, low baseline viral load, and genotype 2 or 3 infection were independent predictors of an RVR and SVR. IP-10 levels decreased 6 weeks into treatment and remained low in patients with an SVR. By contrast, plasma levels of IP-10 rebounded in patients who had detectable HCV RNA after the completion of treatment. Using cutoff IP-10 levels of 150 and 600 pg/mL for predicting an SVR in patients infected with HCV genotype 1 yielded a specificity and sensitivity of 81% and 95%, respectively ConclusionBaseline IP-10 levels are predictive of the response to HCV treatmen

Intestinal Tropism of a Betacoronavirus (Merbecovirus) in Nathusius’s Pipistrelle Bat (Pipistrellus nathusii), Its Natural Host

The emergence of several bat coronavirus-related disease outbreaks in human and domestic animals has fueled surveillance of coronaviruses in bats worldwide. However, little is known about how these viruses interact with their natural hosts. We demonstrate a Betacoronavirus (subgenus Merbecovirus), PN-βCoV, in the intestine of its natural host, Nathusius’s Pipistrelle Bat (Pipistrellus nathusii), by combining molecular and microscopy techniques. Eighty-eight P. nathusii bat carcasses were tested for PN-βCoV RNA by RT-qPCR, of which 25 bats (28%) tested positive. PN-βCoV RNA was more often detected in samples of the intestinal tract than in other sample types. In addition, viral RNA loads were higher in intestinal samples compared to other sample types, both on average and in each individual bat. In one bat, we demonstrated Merbecovirus antigen and PN-βCoV RNA expression in intestinal epithelium and the underlying connective tissue using immunohistochemistry and in situ hybridization, respectively. These results indicate that PN-βCoV has a tropism for the intestinal epithelium of its natural host, Nathusius’s Pipistrelle Bat, and imply that the fecal-oral route is a possible route of transmission.</p

Функціональні зв'язки між ефектами води Нафтуся на канальцеву секреторно-транспортну та імунну системи щурів. Повідомлення 2: Канальцева секреція і параметри спленоцитограми та гемолімфоаденоцитограми

В рамках концепции об общности механизмов функционирования канальцевой секреторно-транспортной и фагоцитарно-лимфоидной систем выявлены существенные связи между скоростью почечной канальцевой секреции и параметрами фагоцитоза, лейкоцитограммы крови, стеноцитогаммы и гемолимфоаденоцитограммы крыс в условиях курсового напаивания их водой Нафтуся per se и в сочетании с цитостатиком или анаболиком.It is shown that increase of canalicular secretion in rats becaused by drinking of water Naftussya accompanied increase massa of haemolymphatic node and contents in its of endothelio-, reticulo-, lymphocytes, eosinophyles and macrophages, blood level lymphocytes, monocytes and segmental nucleare neutrophyles but decrease activity and completion of phagocytose of neutrophyles and level of lymphoblastes in splenocytogramme. The using of cytostatic drug abolishes but anabolic drug potentiates both activating and inhibiting influence of water Naftussya

Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging vi

Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI

Ellipsoidal area mean gravity anomalies - precise computation of gravity anomaly reference fields for remove-compute-restore geoid determination

Gravity anomaly reference fields, required e.g. in remove-compute-restore (RCR) geoid computation, are obtained from global geopotential models (GGM) through harmonic synthesis. Usually, the gravity anomalies are computed as point values or area mean values in spherical approximation, or point values in ellipsoidal approximation. The present study proposes a method for computation of area mean gravity anomalies in ellipsoidal approximation ('ellipsoidal area means') by applying a simple ellipsoidal correction to area means in spherical approximation. Ellipsoidal area means offer better consistency with GGM quasi/geoid heights. The method is numerically validated with ellipsoidal area mean gravity derived from very fine grids of gravity point values in ellipsoidal approximation. Signal strengths of (i) the ellipsoidal effect (i.e., difference ellipsoidal vs. spherical approximation), (ii) the area mean effect (i.e., difference area mean vs. point gravity) and (iii) the ellipsoidal area mean effect (i.e., differences between ellipsoidal area means and point gravity in spherical approximation) are investigated in test areas in New Zealand and the Himalaya mountains. The impact of both the area mean and the ellipsoidal effect on quasigeoid heights is in the order of several centimetres. The proposed new gravity data type not only allows more accurate RCR-based geoid computation, but may also be of some value for the GGM validation using terrestrial gravity anomalies that are available as area mean values

The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats

In all likelihood, it is only a matter of time before our public health system will face a major biological threat, whether intentionally dispersed or originating from a known or newly emerging infectious disease. It is necessary not only to increase our reactive “biodefense,” but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public health communities fully embrace the genomic revolution, and that novel bioinformatic and computing tools necessary to make great strides in our understanding of these novel and emerging threats be developed. Genomics has graduated from a specialized field of science to a research tool that soon will be routine in research laboratories and clinical settings. Because the technology is becoming more affordable, genomics can and should be used proactively to build our preparedness and responsiveness to biological threats. All pieces, including major continued funding, advances in next-generation sequencing technologies, bioinformatics infrastructures, and open access to data and metadata, are being set in place for genomics to play a central role in our public health system