Humans have a close phylogenetic relationship with nonhuman primates (NHPs) and share many physiological parallels, such as highly similar immune systems, with them. Importantly, NHPs can be infected ...with many human or related simian viruses. In many cases, viruses replicate in the same cell types as in humans, and infections are often associated with the same pathologies. In addition, many reagents that are used to study the human immune response cross-react with NHP molecules. As such, NHPs are often used as models to study viral vaccine efficacy and antiviral therapeutic safety and efficacy and to understand aspects of viral pathogenesis. With several emerging viral infections becoming epidemic, NHPs are proving to be a very beneficial benchmark for investigating human viral infections.
Summary
Interferon‐inducible transmembrane (IFITM) proteins are a family of small homologous proteins, localized in the plasma and endolysosomal membranes, which confer cellular resistance to many ...viruses. In addition, several distinct functions have been associated with different IFITM family members, including germ cell specification (IFITM1–IFITM3), osteoblast function and bone mineralization (IFITM5) and immune functions (IFITM1–3, IFITM6). IFITM1–3 are expressed by T cells and recent experiments have shown that the IFITM proteins are directly involved in adaptive immunity and that they regulate CD4+ T helper cell differentiation in a T‐cell‐intrinsic manner. Here we review the role of the IFITM proteins in T‐cell differentiation and function.
Recent studies have identified new T‐cell‐intrinsic roles for the IFITM family in T helper differentiation and atopic and inflammatory disease, which are independent of their functions in cellular resistance to viral infection.
Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the ...pathogenesis of autoimmune diseases that are characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. In this Review, we summarize recent progress in the field of pDC biology, focusing on the molecular mechanisms that regulate the development and functions of pDCs, the pathways involved in their sensing of pathogens and endogenous nucleic acids, their functions at mucosal sites, and their roles in infection, autoimmunity and cancer.
The evolution of the IFN system, the major innate antiviral mechanism of vertebrates, remains poorly understood. According to the detection of type I IFN genes in cartilaginous fish genomes, the ...system appeared 500 My ago. However, the IFN system integrates many other components, most of which are encoded by IFN-stimulated genes (ISGs). To shed light on its evolution, we have used deep RNA sequencing to generate a comprehensive list of ISGs of zebrafish, taking advantage of the high-quality genome annotation in this species. We analyzed larvae after inoculation of recombinant zebrafish type I IFN, or infection with chikungunya virus, a potent IFN inducer. We identified more than 400 zebrafish ISGs, defined as being either directly induced by IFN or induced by the virus in an IFNR-dependent manner. Their human orthologs were highly enriched in ISGs, particularly for highly inducible genes. We identified 72 orthology groups containing ISGs in both zebrafish and humans, revealing a core ancestral ISG repertoire that includes most of the known signaling components of the IFN system. Many downstream effectors were also already present 450 My ago in the common ancestor of tetrapods and bony fish and diversified as multigene families independently in the two lineages. A large proportion of the ISG repertoire is lineage specific; around 40% of protein-coding zebrafish ISGs had no human ortholog. We identified 14 fish-specific gene families containing multiple ISGs, including finTRIMs. This work illuminates the evolution of the IFN system and provides a rich resource to explore new antiviral mechanisms.
Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg virus, Nipah virus, Hendra ...virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory coronavirus (MERS-CoV) and SARS-CoV-2, have been linked back to various bat species. Despite decades of research into bats and the pathogens they carry, the fields of bat virus ecology and molecular biology are still nascent, with many questions largely unexplored, thus hindering our ability to anticipate and prepare for the next viral outbreak. In this Review, we discuss the latest advancements and understanding of bat-borne viruses, reflecting on current knowledge gaps and outlining the potential routes for future research as well as for outbreak response and prevention efforts.
Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date ...analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages.
We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016.
In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval UI 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden.
Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations.
Bill & Melinda Gates Foundation.
Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. ...Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.
The Unequal Pandemic Bambra, Clare; Lynch, Julia; Smith, Katherine E.
06/2021
eBook
Odprti dostop
Rated as a top 10 book about the COVID-19 pandemic by New Statesman: https://www.newstatesman.com/culture/2021/07/best-books-about-covid-19-pandemic
EPDF and EPUB available Open Access under ...CC-BY-NC- ND
It has been claimed that we are ‘all in it together’ and that the COVID-19 virus ‘does not discriminate’.
This accessible, yet authoritative book dispels this myth of COVID-19 as an ‘equal opportunity’ disease, by showing how the pandemic is a syndemic of disease and inequality.
Drawing on international data and accounts, it argues that the pandemic is unequal in three ways: it has killed unequally, been experienced unequally and will impoverish unequally.
These inequalities are a political choice: with governments effectively choosing who lives and who dies, we need to learn from COVID-19 quickly to prevent growing inequality and to reduce health inequalities in the future.
COVID-19 is an unequal pandemic.
The Research and Development (R&D) Blueprint is a World Health Organization initiative to reduce the time between the declaration of a public health emergency and the availability of effective ...diagnostic tests, vaccines, and treatments that can save lives and avert a public health crisis. The scope of the Blueprint extends to severe emerging diseases for which there are insufficient or no presently existing medical countermeasures or pipelines to produce them. In February 2018, WHO held an informal expert consultation to review and update the list of priority diseases, employing a prioritization methodology which uses the Delphi technique, questionnaires, multi-criteria decision analysis, and expert review to identify relevant diseases. The committee determined that, given their potential to cause a public health emergency and the absence of efficacious drugs and/or vaccines, there is an urgent need for accelerated R&D for (in no order of priority) Crimean-Congo haemorrhagic fever, Ebola virus and Marburg virus disease, Lassa fever, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS), Nipah and henipaviral diseases, Rift Valley fever and Zika virus disease. The experts also included “Disease X,” representing the awareness that a previously unknown pathogen could cause a major public health emergency. This report describes the methods and results of the 2018 prioritization review.
•Emerging infectious diseases pose an important threat for humans.•Many of these diseases do not have medical countermeasures.•WHO and partners are tackling this issue to advance product R&D for a set of emerging priority diseases.•A methodology has been developed and externally reviewed in 2016 to identify a priority list of diseases in need of R&D.•This methodology was applied in 2017 and 2018 to review the WHO R&D Blueprint priority list of diseases.
Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection ...(LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.
•Butyrate-producing bacteria abundance is correlated with protection against viral LRTI following allo-HCT.
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