A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Aversion to injection limits acceptability of extended-release naltrexone among homeless, alcohol-dependent patients.

BACKGROUND: Ending homelessness is a major priority of the Department of Veteran Affairs (VA), and alcohol use can be a barrier to stable housing. Clinical trials suggest that depot extended-release naltrexone (XR-NTX) is efficacious in reducing alcohol consumption among alcohol-dependent subjects. METHODS: An open-label, randomized pilot study sought to examine the feasibility and effectiveness of XR-NTX versus oral naltrexone to improve alcohol consumption and housing stability among homeless, alcohol-dependent veterans at the Providence Veteran Affairs Medical Center. RESULTS: Of 215 potential candidates approached over a 16-month recruitment period, only 15 agreed to consider study entry and 7 were randomized. The primary reasons given for refusal were not wanting an injection; fear of needles; and not wanting to change drinking habits. Only 1 participant in the XR-NTX group returned after the first injection. Three participants in the oral naltrexone group attended all 7 visits and had good outcomes. CONCLUSIONS: Although XR-NTX has demonstrated efficacy in reducing heavy drinking, limited acceptance of the injection might reduce its effectiveness among homeless, alcohol-dependent patients

Aversion to Injection Limits Acceptability of Extended-Release Naltrexone Among Homeless, Alcohol-Dependent Patients

BACKGROUND: Ending homelessness is a major priority of the Department of Veteran Affairs (VA), and alcohol use can be a barrier to stable housing. Clinical trials suggest that depot extended-release naltrexone (XR-NTX) is efficacious in reducing alcohol consumption among alcohol-dependent subjects. METHODS: An open-label, randomized pilot study sought to examine the feasibility and effectiveness of XR-NTX versus oral naltrexone to improve alcohol consumption and housing stability among homeless, alcohol-dependent veterans at the Providence Veteran Affairs Medical Center. RESULTS: Of 215 potential candidates approached over a 16-month recruitment period, only 15 agreed to consider study entry and 7 were randomized. The primary reasons given for refusal were not wanting an injection; fear of needles; and not wanting to change drinking habits. Only 1 participant in the XR-NTX group returned after the first injection. Three participants in the oral naltrexone group attended all 7 visits and had good outcomes. CONCLUSIONS: Although XR-NTX has demonstrated efficacy in reducing heavy drinking, limited acceptance of the injection might reduce its effectiveness among homeless, alcohol-dependent patients

A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly-conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems.received: 2014-03-26 accepted: 2014-06-25 published: 2014-06-25status: publishe

Effects of Dietary Fatty Acids on Gene Expression and Biological Processes in Different Tissues of Pigs: A Review

Studies on the influence of dietary components and their effects are fundamental for nutrigenomics, or the study of how nutrients can be cellular sensors, how they affect biological processes and gene expression in different tissues. Lipids are an important source of fatty acids (FA) and energy and are fundamental to biological processes and influence the regulation of transcription. Pigs are excellent model to study nutrigenomics, particularly lipid metabolism because the deposition and composition of FA in their tissues reflect the composition of FA in their diet. Recent studies show that FA supplementation is important in production systems, such as growing and finishing pigs, as it can improve the energy value of the feed, help reduce costs, improve animal welfare, and influence the nutritional value of the meat. Studies show that oleic (OA), linoleic (LA), docosahexaenoic (DHA), and eicosapentaenoic (EPA) acids are associated with the regulation of transcription in tissues such as muscle, liver, adipose tissue, and brain. Other studies indicate that EPA and DHA are associated with changes in specific signaling pathways, altering gene expression and biophysical properties of membranes. This review, therefore, focuses on the current knowledge of the effects of dietary FA on production traits and gene expression.This preprint is made available through Preprints, doi:10.20944/preprints202111.0279.v1. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Effect of Dietary Soybean Oil Inclusion on Liver-Related Transcription Factors in a Pig Model for Metabolic Diseases

The objective of this study was to identify key transcription factors involved in lipid metabolism and immune response related to the differentially expressed genes (DEG) from the liver samples of 35 pig model for metabolic diseases fed diets containing either 1.5 or 3.0% soybean oil (SOY1.5 or SOY3.0). A total of 281 DEG between SOY1.5 and SOY3.0 diets (log2fold-change ≥ 1 or ≤ −1; FDR-corrected p-value < 0.1) were identified, in which 129 were down-regulated and 152 were up-regulated in SOY1.5 group. The functional annotation analysis detected transcription factors linked to lipid homeostasis and immune response, such as RXRA, EGFR, and SREBP2 precursor. These findings demonstrated that key transcription factors related to lipid metabolism could be modulated by dietary inclusion of soybean oil. It could contribute to nutrigenomics research field that aims to elucidate dietary interventions in animal and human health, as well as to drive the food technology and science.This preprint is from Fanalli, S.L.; da Silva, B.P.M.; Gomes, J.D.; Ciconello, F.N.; de Almeida, V.V.; Freitas, F.A.O.; Moreira, G.C.M.; Silva-Vignato, B.; Afonso, J.; Reecy, J.; Koltes, J.; Koltes, D.; Regitano, L.C.D.A.; Baileiro, J.C.D.C.; Freitas, L.; Coutinho, L.L.; Fukumasu, H.; de Alencar, S.M.; Luchiari Filho, A.; Cesar, A.S.M. Effect of Dietary Soybean Oil Inclusion on Liver-Related Transcription Factors in a Pig Model for Metabolic Diseases. Preprints 2022, 2022020149 (doi: 10.20944/preprints202202.0149.v1). This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Transcriptome profile of skeletal muscle using different sources of dietary fatty acids in male pigs

Background Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. Scientific studies that improve our nutrigenomic knowledge about pig and human health through the consumption of pork are of great importance. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. Results The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 531 DEG for SOY vs FO comparison, and 32 DEG for CO vs FO. The enrichment analysis of the DEG lists revealed lipid metabolism, metabolic diseases, and inflammation processes networks, such as "regulation of lipid metabolism: RXR-dependent regulation of lipid metabolism via PPAR, RAR and VDR", “transport HDL-mediated reverse cholesterol transport”, and "TNF- α , IL-1 β induce dyslipidemia and inflammation in obesity and type 2 diabetes in adipocytes". Conclusion The genes identified in this study provided relevant information on biological processes and lipid metabolism pathways. The enrichment of the basal diet with oil containing different FA profiles influenced fatty acid composition of intramuscular fat, blood parameters, and the gene differential expression in metabolic pathways and processes network in skeletal muscle of pigs. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.This preprint is available from Research Square at doi:10.21203/rs.3.rs-1795454/v1.This work is licensed under a Creative Commons Attribution 4.0 International License