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Experimental work on highly pathogenic viruses such as Ebola virus (EBOV) and severe acute respiratory syndrome coronavirus-2 requires high-level biosafety facilities. Here, we provide a detailed step-by-step protocol which details the production and application of replication-incompetent murine leukemia virus-based pseudotyped particles to monitor and quantify the viral entry efficiency in human cell lines under biosafety level-2 conditions. We describe the use of viral particles encoding luciferase gene and the quantification of transduction efficiency by measuring luciferase activity.
Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodid ticks causes B. miyamotoi disease (BMD). To evade the human host´s immune response, relapsing fever borreliae, including B. miyamotoi, produce distinct variable major proteins. Here, we investigated Vsp1, Vlp15/16, and Vlp18 all of which are currently being evaluated as antigens for the serodiagnosis of BMD. Comparative analyses identified Vlp15/16 but not Vsp1 and Vlp18 as a plasminogen-interacting protein of B. miyamotoi. Furthermore, Vlp15/16 bound plasminogen in a dose-dependent fashion with high affinity. Binding of plasminogen to Vlp15/16 was significantly inhibited by the lysine analog tranexamic acid suggesting that the protein–protein interaction is mediated by lysine residues. By contrast, ionic strength did not have an effect on binding of plasminogen to Vlp15/16. Of relevance, plasminogen bound to the borrelial protein cleaved the chromogenic substrate S-2251 upon conversion by urokinase-type plasminogen activator (uPa), demonstrating it retained its physiological activity. Interestingly, further analyses revealed a complement inhibitory activity of Vlp15/16 and Vlp18 on the alternative pathway by a Factor H-independent mechanism. More importantly, both borrelial proteins protect serum sensitive Borrelia garinii cells from complement-mediated lysis suggesting multiple roles of these two variable major proteins in immune evasion of B. miyamotoi.
India has recorded 142,186 deaths over 36 administrative regions placing India third in the world after the US and Brazil for COVID-19 deaths as of 12 December 2020. Studies indicate that south-west monsoon season plays a role in the dynamics of contagious diseases, which tend to peak post-monsoon season. Recent studies show that vitamin D and its primary source Ultraviolet-B (UVB) radiation may play a protective role in mitigating COVID-19 deaths. However, the combined roles of the monsoon season and UVB radiation in COVID-19 in India remain still unclear. In this observational study, we empirically study the respective roles of monsoon season and UVB radiation, whilst further exploring, whether the monsoon season negatively impacts the protective role of UVB radiation in COVID-19 deaths in India. We use a log-linear Mundlak model to a panel dataset of 36 administrative regions in India from 14 March 2020–19 November 2020 (n = 6751). We use the cumulative COVID-19 deaths as the dependent variable. We isolate the association of monsoon season and UVB radiation as measured by Ultraviolet Index (UVI) from other confounding time-constant and time-varying region-specific factors. After controlling for various confounding factors, we observe that a unit increase in UVI and the monsoon season are separately associated with 1.2 percentage points and 7.5 percentage points decline in growth rates of COVID-19 deaths in the long run. These associations translate into substantial relative changes. For example, a permanent unit increase of UVI is associated with a decrease of growth rates of COVID-19 deaths by 33% (= − 1.2 percentage points) However, the monsoon season, mitigates the protective role of UVI by 77% (0.92 percentage points). Our results indicate a protective role of UVB radiation in mitigating COVID-19 deaths in India. Furthermore, we find evidence that the monsoon season is associated with a significant reduction in the protective role of UVB radiation. Our study outlines the roles of the monsoon season and UVB radiation in COVID-19 in India and supports health-related policy decision making in India.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders
(2021)
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.