The IFITMs Inhibit Zika Virus Replication Savidis, George; Perreira, Jill M.; Portmann, Jocelyn M. ...
Cell reports (Cambridge),
06/2016, Letnik:
15, Številka:
11
Journal Article
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Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely ...related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.
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•IFITM3 and IFITM1 inhibit Zika virus infection•IFITM3 can prevent Zika-virus-induced cell death•The IFITMs can halt Zika virus early in the viral life cycle
Savidis et al. find that the IFITMs block Zika virus replication, including that of a recently isolated strain from Cambodia. Importantly, this protection translates into a large reduction in Zika-virus-induced cell death. The authors develop an imaging assay and determine that IFITM3 blocks the very earliest stages of Zika virus infection.
The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous ...functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
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•RNAi and CRISPR/Cas9 screens were used to find flavivirus dependencies•The screens recovered host factors involved in endocytosis and heparin sulfation•The EMC is required by DENV and ZIKV in the early stages of replication•These studies give a systems-wide view of human-flavivirus interactions
Savidis et al. identify DENV and ZIKV dependencies using orthologous RNAi and CRISPR/Cas9 approaches. Multiple host factors involved in endocytosis and transmembrane protein processing, including the endoplasmic reticulum membrane complex (EMC), are important for flaviviral replication. Together, their studies generate a systems-wide view of human-flavivirus interactions.
The green transformation design of traditional hotels aims to reduce the consumption of materials and energy and reduce the emission of harmful substances. Carbon emission, usually used to measure ...energy consumption, is a representative indicator to evaluate the effect of the green transformation process. This paper adopts the emission factor method to measure the carbon emission reduction in the process of hotels’ green transformation from the whole life cycle of hotels, and the results show that: 1) From the perspective of the hotel life cycle, the construction process is the stage with the most carbon emissions. 2) From the perspective of a single hotel, high-star hotels have larger emissions than low-star hotels; 3) As the number of three and four-star hotels far exceeds the five-star hotels, overall, four-star hotels ranked first in total emission reduction. 4) From the perspective of provinces, the hotel industry emission reduction potential of different provinces varies greatly, among which Guangdong, Zhejiang, and Jiangsu provinces are at the top of the list. The future carbon reduction potential of the Chinese hotel industry is very considerable. The content of this paper enriches the research in the field of carbon emission measurement and also provides a reference for the management agency to designate the carbon peaking and carbon neutrality goals of the hotel industry.
Viral myocarditis, an inflammatory disease of the heart, causes significant morbidity and mortality. Type I interferon (IFN)-mediated antiviral responses protect against myocarditis, but the ...mechanisms are poorly understood. We previously identified A Disintegrin And Metalloproteinase domain 9 (ADAM9) as an important factor in viral pathogenesis. ADAM9 is implicated in a range of human diseases, including inflammatory diseases; however, its role in viral infection is unknown. Here, we demonstrate that mice lacking ADAM9 are more susceptible to encephalomyocarditis virus (EMCV)-induced death and fail to mount a characteristic type I IFN response. This defect in type I IFN induction is specific to positive-sense, single-stranded RNA (+ ssRNA) viruses and involves melanoma differentiation-associated protein 5 (MDA5)-a key receptor for +ssRNA viruses. Mechanistically, ADAM9 binds to MDA5 and promotes its oligomerization and thereby downstream mitochondrial antiviral-signaling protein (MAVS) activation in response to EMCV RNA stimulation. Our findings identify a role for ADAM9 in the innate antiviral response, specifically MDA5-mediated IFN production, which protects against virus-induced cardiac damage, and provide a potential therapeutic target for treatment of viral myocarditis.
A balanced pool of hematopoietic stem cells (HSCs) in bone marrow is tightly regulated, and this regulation is disturbed in hematopoietic malignancies such as chronic myeloid leukemia (CML). The ...underlying mechanisms are largely unknown. Here we show that the Lin(-)Sca-1(+)c-Kit(-) (LSK(-)) cell population derived from HSC-containing Lin(-)Sca-1(+)c-Kit(+) (LSK) cells has significantly higher numbers of apoptotic cells. Depletion of LSK cells by radiation or the cytotoxic chemical 5-fluorouracil results in an expansion of the LSK(-) population. In contrast, the LSK(-) population is reduced in CML mice, and depletion of leukemia stem cells (LSCs; BCR-ABL-expressing HSCs) by deleting Alox5 or by inhibiting heat shock protein 90 causes an increase in this LSK(-) population. The transition of LSK to LSK(-) cells is controlled by the Icsbp gene and its downstream gene Lyn, and regulation of this cellular transition is critical for the survival of normal LSK cells and LSCs. These results indicate a potential function of the LSK(-) cells in the regulation of LSK cells and LSCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This article selects the listed companies in China's A-share heavy pollution industry from 2014 to 2018 as samples, uses a random effect model to empirically test the relationship between media ...attention and corporate environmental performance and examines the impacts of local government environmental protection and property nature on that relationship. Results are as follow: (1) Media attention can significantly affect a company's environmental performance. The higher the media attention, the greater the company's supervision and the better its environmental performance. (2) In areas where the government pays less attention to environmental protection, the impact of media on corporate environmental performance is more obvious, but in other areas, the impact of media on environmental performance cannot be reflected; (3) The media attention is very significant for the environmental performance improvement of state-owned enterprises, and it is not obvious in non-state-owned enterprises. (4) A further breakdown of the study found that the role of media attention in corporate environmental performance is only significant in the sample of local governments that have low environmental protection and are state-owned enterprises. This research incorporates the local government's emphasis on environmental protection into the research field of vision, expands the research scope of media and corporate environmental performance, and also provides new clues and evidence for promoting the active fulfillment of environmental protection responsibilities by companies and local governments.
BACKGROUNDInfluenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.METHODSWith the hypothesis that upper ...airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples.ResultsNasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza.ConclusionsOur study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.FundingMassachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) "COVID-19 Expansion for AIRe Program."
China's economy has developed rapidly relying on a large amount of production factors input. It has caused excessive consumption of fossil energy which led to a series of social problems. Although ...Chinese government adopted various measures to reduce energy use, the existence of the energy rebound effect affects the results of energy saving. Therefore, it is necessary to study and carry out the energy rebound effect of various industries in China. This paper works out ten hybrid energy input-output tables (value type) based on the ten input-output tables and energy consumption of the sub-sector from 1987 to 2012. Relying on the supply-driven Ghosh input-output model, this paper calculates the energy rebound effect of industries from 1987 to 2012 in China, and then analyzes the factors which may affect the energy rebound effect value. The results show that: The energy indirect rebound effect is much higher than direct energy rebound effect in most sectors; the higher energy efficiency, the lower direct energy rebound effect; the higher forward linkage degree of industry, the greater indirect rebound effect of energy.
•Independent preparation of a hybrid energy input-output table.•Explore the energy rebound effect values of sectors and influencing factors.•The indirect rebound effect is higher than direct rebound effect in most sectors.•The higher the energy efficiency, the smaller the direct rebound effect.•Industry “forward linkage” degree increases the indirect energy rebound effect.
Dengue is the most prevalent arthropod-borne viral illness in humans with half of the world's population at risk. During early infancy, severe dengue can develop after a primary dengue virus ...infection. There has been a clinical observation that severe dengue during the first year of life is seen only in chubby infants.
We examined the associations between the development of severe dengue and adipose tissue accumulation patterns during the first year of life in a prospective observational clinical study of infants and dengue virus infections. We found that adipose tissue contains two potential targets for dengue virus infection and production- adipocytes and adipose tissue macrophages. During the first year of life, total body adiposity and visceral adipose tissue stores were at their highest levels in early infancy. Early infancy was also characterized by a relative decrease in alternatively activated (anti-inflammatory) macrophages, and a relative increase in circulating pro-inflammatory cytokines.
The data has been used to propose a model where the adipose tissue accumulation pattern and pro-inflammatory environment during early infancy provide the conditions for the potential development of severe dengue in immune-susceptible infants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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