Identification of β2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens

Genome-wide genetic screens are powerful tools to identify genes that act as host factors of viruses. We have applied this technique to analyze the infection of HeLa cells by Vaccinia virus, in an attempt to find genes necessary for infection. Infection of cell populations harboring single gene inactivations resulted in no surviving cells, suggesting that no single gene knock-out was able to provide complete resistance to Vaccinia virus and thus allow cells to survive infection. In the absence of an absolute infection blockage, we explored if some gene inactivations could provide partial protection leading to a reduced probability of infection. Multiple experiments using modified screening procedures involving replication restricted viruses led to the identification of multiple genes whose inactivation potentially increase resistance to infection and therefore cell survival. As expected, significant gene hits were related to proteins known to act in virus entry, such as ITGB1 and AXL as well as genes belonging to their downstream related pathways. Additionally, we consistently found β2-microglobulin, encoded by the B2M gene, among the screening top hits, a novel finding that was further explored. Inactivation of B2M resulted in 54% and 91% reduced VV infection efficiency in HeLa and HAP1 cell lines respectively. In the absence of B2M, while virus binding to the cells was unaffected, virus internalization and early gene expression were significantly diminished. These results point to β2-microglobulin as a relevant factor in the Vaccinia virus entry process.This work was supported by grants ERTA2014-00006, RTA2017-0066 and PID2021-128466OR-I00 funded by Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 as part of the Plan Estatal de Investigación Científica, Desarrollo e Innovación (https://www.ciencia.gob.es) to R.B. A.M. was recipient of a predoctoral contract from Subprograma Estatal de Formación, Programa Estatal de Promoción del Talento y su Empleabilidad en I+D+I, Spain from the Ministerio de Ciencia e Innovación, grant number PRE2018-085415. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Genomic Analysis of West Nile Virus Lineage 1 Detected in Mosquitoes during the 2020–2021 Outbreaks in Andalusia, Spain

Emerging infectious diseases are one of the most important global health challenges because of their impact on human and animal health. The vector-borne West Nile virus (WNV) is transmitted between birds by mosquitos, but it can also infect humans and horses causing disease. The local circulation of WNV in Spain has been known for decades, and since 2010, there have been regular outbreaks in horses, although only six cases were reported in humans until 2019. In 2020, Spain experienced a major outbreak with 77 human cases, which was followed by 6 additional cases in 2021, most of them in the Andalusian region (southern Spain). This study aimed to characterize the genomes of the WNV circulating in wild-trapped mosquitoes during 2020 and 2021 in Andalusia. We sequenced the WNV consensus genome from two mosquito pools and carried out the phylogenetic analyses. We also compared the obtained genomes with those sequenced from human samples obtained during the outbreak and the genomes obtained previously in Spain from birds (2007 and 2017), mosquitoes (2008) and horses (2010) to better understand the eco-epidemiology of WNV in Spain. As expected, the WNV genomes recovered from mosquito pools in 2020 were closely related to those recovered from humans of the same outbreak. In addition, the strain of WNV circulating in 2021 was highly related to the WNV strain that caused the 2020 outbreak, suggesting that WNV is overwintering in the area. Consequently, future outbreaks of the same strain may occur in in the future.This research was funded by the Research State Agency projects PGC2018-095704-B-I00 and PID2020-118921RJ-I00Instituto de Salud Carlos III Project PI19CIII_00014European Commission—NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global+)

Multivalvular Endocarditis: A Rare Condition with Poor Prognosis.

Background. Infective endocarditis (IE) is a severe condition. Our aim was to describe the profile and prognosis of patients with multivalvular infective endocarditis (MIE) and compare them to single-valve IE (SIE). Methods. We used a retrospective analysis of the Spanish IE Registry (2008−2020). Results. From 4064 definite cases of valvular IE, 577 (14.2%) had MIE. In patients with MIE, the most common locations were mitral (552, 95.7%) and aortic (550, 95.3%), with mitral-aortic involvement present in 507 patients (87.9%). The most common etiologies were S. viridans (192, 33.3%) and S. aureus (113, 19.6%). MIE involved only native valves in 450 patients (78.0%). Compared with patients with SIE, patients with MIE had a similar age (69 vs. 67 years, respectively, p = 0.27) and similar baseline characteristics, but were more frequently men (67.1% vs. 72.9%, p = 0.005) and had a higher incidence of intracardiac complications (36.2% vs. 50.4%, p < 0.001), heart failure (42.7% vs. 52.9%, p < 0.001), surgical indication (67.7 vs. 85.1%, p < 0.001), surgery (46.3% vs. 56.3%), and in-hospital mortality (26.9% vs. 34.3%, p < 0.001). MIE was an independent predictor of in-hospital mortality (odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1−1.7, p = 0.004) but did not have an independent association with 1-year mortality (OR 1.1, 95% CI 0.9−1.4, p = 0.43). Conclusions. About one-seventh of the valvular IE patients had MIE, mainly due to mitral-aortic involvement. MIE is associated with a poor in-hospital prognosis. An early diagnosis and treatment of IE might avoid its spread to a second valve

Presenteeism in nurses: comparative study of Spanish, Portuguese and Brazilian nurses

Aim:To compare presenteeism levels among three samples of nurses and to identify the relationship between presenteeism andsociodemographic and professional characteristics.Background:Presenteeism (going to work ill) is a phenomenon studied from different perspectives, and it has become especially important duringthe current COVID-19 outbreak; its connection to high healthcare costs, patient safety breaches and negative nurse well-being has been proved.Introduction:The nursing profession is particularly associated with caring for the culture of teamwork, loyalty to colleagues and professionalidentity. This condition enhances the ‘super nurse phenomenon’, even though nurses do not feel physically and psychologically able to work.Methods:A multicentre, cross-sectional study was conducted in three different country contexts: Oviedo (Spain), Porto (Portugal) andS~ao Paulo (Brazil). Nurses performing functions in hospitals and primary health care were enrolled. Informed consent and datacollection questionnaires were hand delivered. The Stanford Presenteeism Scale-6 was applied.Results:A total of 659 nurses participated. Portuguese nurses showed greater prevalence of presenteeism, followed by Brazilian andSpanish nurses. Younger nurses with less professional experience presented lower levels of presenteeism but greater psychologicalcommitment. Male participants showed lower capacity to complete work when ill than female participants.Conclusions:Age and length of professional experience proved to be significant predictors of total presenteeism, although onlyprofessional experience revealed statistical significance in the adjusted model.Implications for Nursing and Health Policy:The knowledge of this phenomenon among nurses highlights the need for thedevelopment of strategies in the curriculum of nursing students and organizations. Resilience and ergonomic training should be appliedin the training programmes of the students and reinforced by the health centre managers. It is essential that healthcare systems design worksite wellness programmes that pursue greater physical and mental well-being for healthcare professionals.info:eu-repo/semantics/publishedVersio