Weerapan Khovidhunkit
Jul 1, 2004; 45:1169-1196
Thematic Reviews

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

Julia Knöckel
Dec 22, 2020; 0:RA120.002432v1-mcp.RA120.002432
Research

Laura F Fielden
Nov 11, 2020; 0:RA120.002370v1-mcp.RA120.002370
Research

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response, and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria-associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an up-regulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1β secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

Modulation of the host cell is integral to the survival and replication of microbial pathogens. Several intracellular bacterial pathogens deliver bacterial proteins, termed ‘effector proteins’ into the host cell during infection by sophisticated protein translocation systems, which manipulate cellular processes and functions. The functional contribution of individual effectors is poorly characterised, particularly in intracellular bacterial pathogens with large effector protein repertoires. Technical caveats have limited the capacity to study these proteins during a native infection, with many effector proteins having only been demonstrated to be translocated during over-expression of tagged versions. Here we developed a novel strategy to examine effector proteins in the context of infection. We coupled a broad, unbiased proteomics-based screen with organelle purification to study the host-pathogen interactions occurring between the host cell mitochondrion and the Gram-negative, Q fever pathogen Coxiella burnetii. We identify 4 novel mitochondrially-targeted C. burnetii effector proteins, renamed Mitochondrial Coxiella effector protein (Mce) B to E. Examination of the subcellular localisation of ectopically expressed proteins confirmed their mitochondrial localisation, demonstrating the robustness of our approach. Subsequent biochemical analysis and affinity enrichment proteomics of one of these effector proteins, MceC, revealed the protein localises to the inner membrane and can interact with components of the mitochondrial quality control machinery. Our study adapts high-sensitivity proteomics to study intracellular host-pathogen interactions, providing a robust strategy to examine the sub-cellular localisation of effector proteins during native infection. This approach could be applied to a range of pathogens and host cell compartments to provide a rich map of effector dynamics throughout infection.

Sporozoites are a motile form of malaria-causing Plasmodium falciparum parasites that migrate from the site of transmission in the dermis through the bloodstream to invade hepatocytes. Sporozoites interact with many cells within the host, but the molecular identity of these interactions and their role in the pathology of malaria is poorly understood. Parasite proteins that are secreted and embedded within membranes are known to be important for these interactions, but our understanding of how they interact with each other to form functional complexes is largely unknown. Here, we compile a library of recombinant proteins representing the repertoire of cell surface and secreted proteins from the P. falciparum sporozoite and use an assay designed to detect extracellular interactions to systematically identify complexes. We identify three protein complexes including an interaction between two components of the p24 complex that is involved in the trafficking of glycosylphosphatidylinositol (GPI)-anchored proteins through the secretory pathway. Plasmodium parasites lacking either gene are strongly inhibited in the establishment of liver stage infections. These findings reveal an important role for the p24 complex in malaria pathogenesis and show that the library of recombinant proteins represents a valuable resource to investigate P. falciparum sporozoite biology.

A new paper analyzes three decades of fatalities around the world and predicts how "superbugs" will affect human health in the future

Title: 'Bagpipe' Lung Infection Kills Piper
Category: Health News
Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/23/2016 12:00:00 AM

Title: Five More Cases of Local Zika Infection Reported in Florida
Category: Health News
Created: 8/24/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Title: Gene Test Might Quickly ID Baby's Infection
Category: Health News
Created: 8/23/2016 12:00:00 AM
Last Editorial Review: 8/24/2016 12:00:00 AM

Title: New Case of Local Zika Infection Reported in Florida
Category: Health News
Created: 8/25/2016 12:00:00 AM
Last Editorial Review: 8/26/2016 12:00:00 AM

Title: FDA Warns of Serious Genital Infection With Diabetes Meds
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM

Title: Climate Change Hiking Danger of Flesh-Eating Bacteria Infections
Category: Health News
Created: 8/23/2019 12:00:00 AM
Last Editorial Review: 8/26/2019 12:00:00 AM

Title: Confirmed Case of Coronavirus Reinfection Reported
Category: Health News
Created: 8/25/2020 12:00:00 AM
Last Editorial Review: 8/25/2020 12:00:00 AM

Title: You're Vaccinated But Get a Breakthrough Infection: What Next?
Category: Health News
Created: 8/26/2021 12:00:00 AM
Last Editorial Review: 8/26/2021 12:00:00 AM

Title: COVID Breakthrough Infections More Likely in People Living With HIV
Category: Health News
Created: 6/8/2022 12:00:00 AM
Last Editorial Review: 6/9/2022 12:00:00 AM

Title: Yeast infections vs. STDs in Men and Women
Category: Diseases and Conditions
Created: 1/8/2020 12:00:00 AM
Last Editorial Review: 7/29/2022 12:00:00 AM

Title: Vaccines Have Slashed Rates of HPV Infection in Young American Women
Category: Health News
Created: 8/22/2022 12:00:00 AM
Last Editorial Review: 8/23/2022 12:00:00 AM

Title: Hepatitis C Infection Can Kill, But Less Than a Third of Patients Get Treatment
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/10/2022 12:00:00 AM

Extract

With a disproportionate burden of tuberculosis (TB) amongst migrants in Europe [1], Burman et al. [2] have highlighted the pressing need for alternative approaches to make TB infection (TBI) screening comprehensive and accessible. Across high-income Organisation for Economic Co-operation and development countries, a median of 52% of TB cases occur in foreign-born individuals, who are at their highest risk of developing TB disease within the first 5 years of migration [3]. Molecular epidemiological studies indicate that the majority of these cases occur as a result of TBI reactivation, often acquired overseas [4]. Within the UK, overseas-born migrants have a 14-fold higher TB incidence than UK-born individuals [5]. The World Health Organization therefore recommends that migrants from countries with a high TB burden may be prioritised for TBI screening [6, 7].

Extract

In cystic fibrosis (CF), Pseudomonas aeruginosa acquisition represents a turning point in disease progression. The presence of chronic P. aeruginosa infection is associated with worsening lung function and increased risk of earlier death, whereas treatment substantially improves lung function and survival [1, 2]. Efforts to diagnose and eradicate early P. aeruginosa provide lasting benefits for children with CF [3, 4]. However, the timing of infection varies considerably between individuals with CF, treatment centres [5, 6], and different birth cohorts of people with the disease [7, 8].

Background

Pseudomonas aeruginosa is a common pathogen that contributes to progressive lung disease in cystic fibrosis (CF). Genetic factors other than CF-causing CFTR (CF transmembrane conductance regulator) variations contribute ~85% of the variation in chronic P. aeruginosa infection age in CF according to twin studies, but the susceptibility loci remain unknown. Our objective is to advance understanding of the genetic basis of host susceptibility to P. aeruginosa infection.

Background

Control of latent tuberculosis infection (LTBI) is a priority in the World Health Organization strategy to eliminate TB. Many high-income, low TB incidence countries have prioritised LTBI screening and treatment in recent migrants. We tested whether a novel model of care, based entirely within primary care, was effective and safe compared to secondary care.

Certain strains of E. coli are capable of causing severe disease, by rapidly spreading through the human digestive system, wreaking havoc throughout the bloodstream, and eventually damaging the delicate kidneys. That's the situation right now during a large outbreak in Alberta, with hundreds of children now affected.

Zapping the skin with electricity could stop bacteria that live there harmlessly from entering the body and causing blood poisoning

Montana public health officials are investigating an outbreak of infections caused by Salmonella. The Cascade City-County Health Department in Great Falls is reporting that six students at Sacajawea and Valley View elementary schools have tested positive for the pathogen. A staff member at another school has also tested positive. There... Continue Reading

Une découverte biochimique intrigante pourrait permettre d’identifier rapidement les patients à haut risque.

Zapping the skin with electricity could stop bacteria that live there harmlessly from entering the body and causing blood poisoning

In the past 24 hours, an additional surge in medlinkdengue/medlink patients has pushed the total number of cases in Bihar beyond 13,000, stated officials (!--ref1--).

The key steps that healthcare teams can take to identify and treat more sexually transmitted infections (STIs) have been identified. The 1,348 participants

Developing a nonsurgical medlinkdrug delivery system/medlink that will enable the controlled delivery of medlinkantibiotics/medlink that helps

India has been lauded by the World Health Organization for successfully eradicating trachoma, a bacterial eye infection that can lead to medlinkblindness/medlink.

Two individuals in the United States who received lung transplants have contracted a lethal Legionella bacterial infection, according to the Centers for Disease Control and Prevention (!--ref1--).

Gut bacteria play an important role in determining the severity of viral infections like chikungunya. Faulty gut microbiome increase the severity of illness

BJP President Amit Shah infected with swine flu virus. He got admitted to the All India Institute of Medical Sciences (AIIMS) on Wednesday for treatment.

In Europe in 2022, around 1,300 locally acquired human cases of medlinkWest Nile virus/medlink infection have been recorded (!--ref1--). They

The medlinkEbola virus/medlink generates and utilizes intercellular tunnels, aiding its movement between cells while evading treatments. (!--ref1--)

Australian health officials have alerted the public to a rise in medlinkmpox/medlink cases in New South Wales (NSW) (!--ref1--), urging residents to be vigilant for symptoms of the disease.

India has made remarkable strides in the fight against medlinkHIV/AIDS/medlink, with the country's annual medlinkHIV infections/medlink dropping

Artificial intelligence or machine learning may soon be a valuable tool for ophthalmologists in diagnosing infectious keratitis, a leading cause of corneal blindness globally.

Vesicoureteral reflux (VUR) is a congenital condition most common in infants and young children. The urine flows backward from the bladder to one or both ureters and sometimes to the kidneys.

In China's Jiangsu province, a human infection with the H10N3 strain of avian influenza has been detected, said the National Health Commission (NHC).

In China, three people have tested positive for H5N6 bird flu. The Guangdong Provincial Health Commission, in a statement on Thursday said that a 52-year-old

Herbal extracts could treat Bartonella infections effectively. A new research funded in part by the Bay Area Lyme Foundation that tested the antimicrobial