scholarly journals The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4395
Author(s):  
René Lutter ◽  
Annemarie Teitsma-Jansen ◽  
Esther Floris ◽  
Saeeda Lone-Latif ◽  
Abilash Ravi ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Viral Clearance ◽  
Innate Immune ◽  
Nasal Lavage ◽  
Health Concern ◽  
Interferon Response ◽  
Viral Gene ◽  
Duration Of Symptoms ◽  
Rhamnogalacturonan I ◽  
Viral Responses

Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (−20%) and duration (−25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.

scholarly journals Human TRIM5α: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 320 ◽  
Author(s):  
Alexandra P. M. Cloherty ◽  
Anusca G. Rader ◽  
Brandon Compeer ◽  
Carla M. S. Ribeiro
Keyword(s):  
Therapeutic Potential ◽  
Innate Immune ◽  
Health Concern ◽  
Restriction Factor ◽  
Viral Reservoirs ◽  
Minimal Restriction ◽  
Immunodeficiency Virus ◽  
A Cell ◽  
Species Specific ◽  
Hiv 1

Human immunodeficiency virus-1 (HIV-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. Combination antiretroviral treatment is highly effective, but HIV-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. It is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for HIV-1. It has been long accepted that the restriction factor tripartite motif protein 5 isoform alpha (TRIM5α) restricts HIV-1 infection in a species-specific manner, with rhesus macaque TRIM5α strongly restricting HIV-1, and human TRIM5α having a minimal restriction capacity. However, several recent studies underscore human TRIM5α as a cell-dependent HIV-1 restriction factor. Here, we present an overview of the latest research on human TRIM5α and propose a novel conceptualization of TRIM5α as a restriction factor with a varied portfolio of antiviral functions, including mediating HIV-1 degradation through autophagy- and proteasome-mediated mechanisms, and acting as a viral sensor and effector of antiviral signaling. We have also expanded on the protective antiviral roles of autophagy and outline the therapeutic potential of autophagy modulation to intervene in chronic HIV-1 infection.

scholarly journals First molecular detection of hepatitis E virus genome in camel and pig faecal samples in Ethiopia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Fufa Dawo Bari ◽  
Haimanot Belete Wodaje ◽  
Umer Said ◽  
Hika Waktole ◽  
Melaku Sombo ◽  
...  
Keyword(s):  
Public Health ◽  
Hepatitis E Virus ◽  
Addis Ababa ◽  
Hepatitis E ◽  
Human Infection ◽  
Health Concern ◽  
Universal Primers ◽  
Viral Gene ◽  
Public Health Importance ◽  
Faecal Samples

Abstract Background Hepatitis E is an enteric and zoonotic disease caused by hepatitis E virus (HEV) that is mainly transmitted via the faecal-oral route through contaminated food or the environment. The virus is an emerging infectious agent causing acute human infection worldwide. A high seroprevalence of the disease was reported in pregnant women in Addis Ababa, Ethiopia, raising significant public health concern. The presence of HEV specific antibodies were also reported in dromedary camels in the country; however, the infectious virus and/or the viral genome have not been demonstrated to date in animal samples. Methods To address this gap, a total of 95 faecal samples collected from both apparently healthy pigs of uncharacterised types (50 samples) in Burayu and Addis Ababa areas and camels (Camelus dromedarius, 45 samples) in west Hararghe were screened for the presence of HEV genome using universal primers in a fully nested reverse transcription polymerase chain reaction (nRT-PCR). The protocol is capable of detecting HEV in faecal samples from both pigs and camels. Results The nRT-PCR detected HEV genes in six (12%) pig faecal samples and one camel sample (2.2%). Therefore, the results indicate that HEV is circulating in both pigs and camels in Ethiopia and these animals and their products could serve as a potential source of infection for humans. Conclusion The detection of HEV in both animals could raise another concern regarding its public health importance as both animals’ meat and camel milk are consumed in the country. Further studies to determine the prevalence and distribution of the virus in different animals and their products, water bodies, food chain, and vegetables are warranted, along with viral gene sequencing for detailed genetic characterisation of the isolates circulating in the country. This information is critically important to design and institute appropriate control and/or preventive measures.

Prevalence and Predictors of Overweight and Obesity among Military Personnel with Low Socio-Economic Status in Kuala Lumpur

2021 ◽  
Author(s):  
Nik Qistina Nik Abd Rahim ◽  
Nor Afiah Mohd Zulkefli ◽  
Mohd Arshil Moideen
Keyword(s):  
Dietary Intake ◽  
Water Intake ◽  
Low Socioeconomic Status ◽  
Overweight And Obesity ◽  
Health Concern ◽  
Plain Water ◽  
Low Ses ◽  
Kuala Lumpur ◽  
History Of ◽  
Army Personnel

Abstract Background: It is a major public health concern when 52% of adults worldwide were overweight and obese. Military institutions worldwide were included, which led to negative impacts on the overall combat readiness due to the obesity-associated-diseases. This study determined the prevalence and predictors of overweight and obesity among the low socioeconomic status (SES) army personnel in Kuala Lumpur. Methods: A cross-sectional study involving 772 low SES army personnel in Kuala Lumpur was conducted. Online questionnaires were distributed while anthropometric measurements’ data were obtained from Military Lifetime Health Record (MLHR) system with BMI of > 25kg/m2 as the outcome. Data analysed using SPSS version 23.0 (descriptive and inferential statistics). Results: The median age of the respondents was 30 (IQR=7) years. The prevalence of overweight and obese army personnel was 41.1% (95%CI:37.6-44.6). The predictors found were being married (AOR:2.026,95%CI:1.318-3.113), secondary education (AOR:2.545,95%CI:1.245-5.203), Lance Corporal (AOR:1.994,95%CI:1.061-3.748), Corporal (AOR:2.814,95%CI:1.578-5.020), Sergeant (AOR:4.174,95%CI:2.076-8.390), past injury (AOR:1.879,95%CI: 1.191-2.965), history of obese sibling (AOR:1.737,95%CI:1.013-2.973), history of obese parent (AOR:3.344,95%CI:1.965-5.688), history of obese grandparent (AOR:11.321,95%CI:2.207-58.072), poor knowledge on dietary intake (AOR:1.524,95%CI:1.077-2.157), less than 2 litres daily plain water intake (AOR:1.606,95%CI:1.166-2.210). Conclusions: Knowledge on dietary intake and plain water intake are the two modifiable predictors for overweight and obesity found in this study, while the other nine predictors are non-modifiable. Understanding on issues surrounding the low SES group will help the strategic level in planning for future comprehensive interventions on overweight and obesity, specifically targeting on those predictors.

scholarly journals Ifit1 regulates norovirus infection and enhances the interferon response in murine macrophage-like cells

2019 ◽  
Vol 4 ◽  
pp. 82 ◽  
Author(s):  
Harriet V. Mears ◽  
Edward Emmott ◽  
Yasmin Chaudhry ◽  
Myra Hosmillo ◽  
Ian G. Goodfellow ◽  
...  
Keyword(s):  
Viral Protein ◽  
Innate Immune ◽  
Interferon Response ◽  
Genome Replication ◽  
Murine Norovirus ◽  
Murine Macrophage ◽  
Viral Protein Synthesis ◽  
Viral Translation ◽  
Double Stranded Rna

Background: Norovirus, also known as the winter vomiting bug, is the predominant cause of non-bacterial gastroenteritis worldwide. Disease control is predicated on a robust innate immune response during the early stages of infection. Double-stranded RNA intermediates generated during viral genome replication are recognised by host innate immune sensors in the cytoplasm, activating the strongly antiviral interferon gene programme. Ifit proteins (interferon induced proteins with tetratricopeptide repeats), which are highly expressed during the interferon response, have been shown to directly inhibit viral protein synthesis as well as regulate innate immune signalling pathways. Ifit1 is well-characterised to inhibit viral translation by sequestration of eukaryotic initiation factors or by directly binding to the 5' terminus of foreign RNA, particularly those with non-self cap structures. However, noroviruses have a viral protein, VPg, covalently linked to the 5' end of the genomic RNA, which acts as a cap substitute to recruit the translation initiation machinery. Methods: Ifit1 knockout RAW264.7 murine macrophage-like cells were generated using CRISPR-Cas9 gene editing. These cells were analysed for their ability to support murine norovirus infection, determined by virus yield, and respond to different immune stimuli, assayed by quantitative PCR. The effect of Ifit proteins on norovirus translation was also tested in vitro. Results: Here, we show that VPg-dependent translation is completely refractory to Ifit1-mediated translation inhibition in vitro and Ifit1 cannot bind the 5' end of VPg-linked RNA. Nevertheless, knockout of Ifit1 promoted viral replication in murine norovirus infected cells. We then demonstrate that Ifit1 promoted interferon-beta expression following transfection of synthetic double-stranded RNA but had little effect on toll-like receptor 3 and 4 signalling. Conclusions: Ifit1 is an antiviral factor during norovirus infection but cannot directly inhibit viral translation. Instead, Ifit1 stimulates the antiviral state following cytoplasmic RNA sensing, contributing to restriction of norovirus replication.

scholarly journals BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors

2018 ◽  
Author(s):  
Timo Reisländer ◽  
Emilia Puig Lombardi ◽  
Florian J. Groelly ◽  
Ana Miar ◽  
Manuela Porru ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Cycle Progression ◽  
Parp Inhibitors ◽  
Innate Immune ◽  
Interferon Response ◽  
Acute Response ◽  
Cycle Arrest ◽  
Dna Replication And Repair ◽  
Sting Pathway

Heterozygous germline mutations in BRCA2 predispose to breast and ovarian cancer. Contrary to non-cancerous cells, where BRCA2 deletion causes cell cycle arrest or cell death, BRCA2 inactivation in tumors is associated with uncontrolled cell proliferation. We set out to investigate this conundrum by exploring modalities of cell adaptation to loss of BRCA2 and focused on genome-wide transcriptome alterations. Human cells in which BRCA2 expression was inhibited using a doxycycline (DOX)-inducible shRNA for 4 or 28 days were subjected to RNA-seq analyses. Gene sets differentially expressed in BRCA2-deficient versus -proficient cells revealed a biphasic response to BRCA2 abrogation. The early, acute response consisted of downregulation of genes involved in cell cycle progression, DNA replication and repair and was associated with cell cycle arrest in G1. Surprisingly, the late, chronic response consisted predominantly of upregulation of innate immune response genes controlled by interferon. Activation of the cGAS-STING pathway detected in these cells further substantiated the concept that long-term BRCA2 abrogation triggers cell-intrinsic immune signaling. Importantly, we found that treatment with PARP inhibitors stimulated the interferon response in cells and tumors lacking BRCA2. We propose that PARP inhibitors may suppress growth of BRCA2-deficient cells and tumors, in part, by activating interferon signaling.

scholarly journals A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP

2009 ◽  
Vol 206 (9) ◽  
pp. 1899-1911 ◽  
Author(s):  
Sarah M. McWhirter ◽  
Roman Barbalat ◽  
Kathryn M. Monroe ◽  
Mary F. Fontana ◽  
Mamoru Hyodo ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Map Kinases ◽  
Second Messenger ◽  
Innate Immune ◽  
Guanosine Monophosphate ◽  
Host Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I

The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.

RNA sensors as a mechanism of innate immune evasion among SARS-CoV2, HIV and Nipah viruses

2021 ◽  
Vol 22 ◽  
Author(s):  
Dalia Cicily Kattiparambil Dixon ◽  
Chameli Ratan ◽  
Bhagyalakshmi Nair ◽  
Sabitha Mangalath ◽  
Rachy Abraham ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
Interferon Response ◽  
Host Immune System ◽  
Type I ◽  
Adaptive Responses ◽  
Rna Sensors

: Innate immunity is the first line of defence elicited by the host immune system to fight against invading pathogens such as viruses and bacteria. From this elementary immune response, the more complex antigen-specific adaptive responses are recruited to provide a long-lasting memory against the pathogens. Innate immunity gets activated when the host cell utilizes a diverse set of receptors known as pattern recognition receptors (PRR) to recognize the viruses that have penetrated the host and respond with cellular processes like complement system, phagocytosis, cytokine release and inflammation and destruction of NK cells. Viral RNA or DNA or viral intermediate products are recognized by receptors like toll-like receptors(TLRs), nucleotide oligomerization domain(NOD)-like receptors (NLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) thereby, inducing type I interferon response (IFN) and other proinflammatory cytokines in infected cells or other immune cells. But certain viruses can evade the host innate immune response to replicate efficiently, triggering the spread of the viral infection. The present review describes the similarity in the mechanism chosen by viruses from different families -HIV, SARS-CoV2 and Nipah viruses to evade the innate immune response and how efficiently they establish the infection in the host. The review also addresses the stages of developments of various vaccines against these viral diseases and the challenges encountered by the researchers during vaccine development.

scholarly journals Yogurt Consumption Is Associated with Better Dietary Intake and Diet Quality in School-aged Children (P18-112-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yong Zhu ◽  
Jessica Smith ◽  
Valerie Benoit ◽  
Neha Jain ◽  
Vipra Vanage ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Diet Quality ◽  
The United States ◽  
Healthy Eating Index ◽  
Health Concern ◽  
School Aged Children ◽  
Funding Sources ◽  
Health And Nutrition ◽  
Calcium Magnesium ◽  
Total Fat

Abstract Objectives To assess associations between yogurt consumption and dietary intake as well as diet quality in school-aged children in the United States. Methods A total of 3709 children aged 6–12 years from the National Health and Nutrition Examination Survey 2011–2012, 2013–2014 and 2015–2016 were included in the study. Day 1 dietary data were used to determine yogurt consumption status, energy and nutrient intake. Healthy Eating Index 2015 (HEI-2015) was used as a measure of diet quality. Multiple linear regression analyses for surveys were conducted to estimate associations between yogurt consumption and dietary intake, as well as diet quality, adjusting for sociodemographic characteristics. Results About 9% of children aged 6–12 years were yogurt eaters. Compared to non-eaters, children who reported yogurt consumption had significantly higher intake of calcium, magnesium, phosphorus, potassium, total sugar and carbohydrate, as well as significantly less intake of total fat and sodium (P < 0.05 for all). There were no significant differences on intake of added sugar and total energy intake. HEI-2015 total score, as well as sub scores for greens and beans, whole fruit, dairy, and sodium were significantly higher in yogurt eaters than non-eaters (P < 0.05 for all). Conclusions Consumption of yogurt is associated with increased intake of several key vitamins and minerals, including nutrients of public health concern such as calcium and potassium, in school-aged children. Yogurt consumption is also associated with better diet quality in this population. Funding Sources The study was funded by General Mills, Inc.

Mitochondrial Quality Control and Restraining Innate Immunity

2020 ◽  
Vol 36 (1) ◽  
pp. 265-289
Author(s):  
Andrew T. Moehlman ◽  
Richard J. Youle
Keyword(s):  
Innate Immunity ◽  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Interferon Response ◽  
Mitochondrial Quality Control ◽  
Selective Autophagy ◽  
Eukaryotic Organisms ◽  
And Function

Maintaining mitochondrial health is essential for the survival and function of eukaryotic organisms. Misfunctioning mitochondria activate stress-responsive pathways to restore mitochondrial network homeostasis, remove damaged or toxic proteins, and eliminate damaged organelles via selective autophagy of mitochondria, a process termed mitophagy. Failure of these quality control pathways is implicated in the pathogenesis of Parkinson's disease and other neurodegenerative diseases. Impairment of mitochondrial quality control has been demonstrated to activate innate immune pathways, including inflammasome-mediated signaling and the antiviral cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)–regulated interferon response. Immune system malfunction is a common hallmark in many neurodegenerative diseases; however, whether inflammation suppresses or exacerbates disease pathology is still unclear. The goal of this review is to provide a historical overview of the field, describe mechanisms of mitochondrial quality control, and highlight recent advances on the emerging role of mitochondria in innate immunity and inflammation.

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