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MBio Aug 2023Interferon (IFN) represents a well-known component of antiviral immunity that has been studied extensively for its mechanisms of action and therapeutic potential when... (Review)
Review
Interferon (IFN) represents a well-known component of antiviral immunity that has been studied extensively for its mechanisms of action and therapeutic potential when antiviral treatment options are limited. Specifically in the respiratory tract, IFNs are induced directly on viral recognition to limit the spread and transmission of the virus. Recent focus has been on the IFNλ family, which has become an exciting focus in recent years for its potent antiviral and anti-inflammatory activities against viruses infecting barrier sites, including the respiratory tract. However, insights into the interplay between IFNλs and other pulmonary infections are more limited and suggest a more complex role, potentially detrimental, than what was seen during viral infections. Here, we review the role of IFNλs in pulmonary infections, including viral, bacterial, fungal, and multi-pathogen super-infections, and how this may impact future work in the field.
Topics: Humans; Interferons; Antiviral Agents; Pneumonia
PubMed: 37278532
DOI: 10.1128/mbio.02850-22 -
Microbial Pathogenesis Aug 2023Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma... (Review)
Review
INTRODUCTION
Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1.
METHODS
A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used.
RESULTS
We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment.
CONCLUSIONS
Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.
Topics: Humans; Child, Preschool; Child; Herpesvirus 1, Human; Glioblastoma; Encephalitis, Herpes Simplex; Herpes Simplex; Antiviral Agents; Tumor Microenvironment
PubMed: 37343897
DOI: 10.1016/j.micpath.2023.106211 -
Acta Dermatovenerologica Alpina,... Dec 2023Autoimmune blistering skin diseases (AIBDs) encompass several heterogeneous conditions clinically characterized by blisters and erosions on the skin and mucous membranes... (Review)
Review
Autoimmune blistering skin diseases (AIBDs) encompass several heterogeneous conditions clinically characterized by blisters and erosions on the skin and mucous membranes and are immunopathologically characterized by autoantibodies against structural proteins of the skin. Those proteins are responsible for the intercellular contact between epidermal keratinocytes and adhesion of the basal keratinocytes to the dermis. Therefore, AIBDs are divided into two main groups: intraepidermal (the pemphigus group) and subepidermal (the pemphigoid) groups. The diagnostic methods for AIBDs have made tremendous progress in the last 2 decades due to the availability of standardized serological assays that allow precise diagnosis in most patients. If left untreated, these diseases are potentially life-threatening due to superinfections and loss of body fluids, and in some severe cases due to restricted food intake. Based on the available literature, this paper provides an overview of the clinical and immunopathological characteristics of the most common AIBDs.
Topics: Humans; Autoantibodies; Autoimmune Diseases; Blister; Pemphigoid, Bullous; Pemphigus
PubMed: 38126096
DOI: No ID Found -
Antibiotics (Basel, Switzerland) Mar 2024Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for... (Review)
Review
Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks-hepatic/renal dysfunction, intermediate effects-concomitant superinfections, and long-term risks-potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment.
PubMed: 38534707
DOI: 10.3390/antibiotics13030272 -
Retrovirology Aug 2023Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated...
BACKGROUND
Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect.
RESULTS
We developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed.
CONCLUSIONS
The mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx.
Topics: Humans; Animals; Swine; Superinfection; Gammaretrovirus; Genes, env; Phenotype; RNA, Viral
PubMed: 37605152
DOI: 10.1186/s12977-023-00630-x -
Viruses Sep 2023The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear....
BACKGROUND
The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients.
METHODS
Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant was assessed.
RESULTS
The incidence of KPC-producing and/or carbapenem-resistant rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing and/or carbapenem-resistant occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24-1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18-12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43-9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40-0.72) were the features most strongly associated with in-hospital mortality.
CONCLUSIONS
Although KPC-producing and/or carbapenem-resistant rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.
Topics: Adult; Humans; Carbapenems; Anti-Bacterial Agents; Retrospective Studies; Prevalence; Superinfection; COVID-19; SARS-CoV-2; Klebsiella pneumoniae; Sepsis
PubMed: 37766340
DOI: 10.3390/v15091934 -
Frontiers in Veterinary Science 2023
PubMed: 38094500
DOI: 10.3389/fvets.2023.1329073 -
BioRxiv : the Preprint Server For... Aug 2023Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is the only phage protein required for exclusion by the SieA system, and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants were isolated that overcome the SieA block, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in target specificity. Our data are consistent with a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.
PubMed: 37645741
DOI: 10.1101/2023.08.15.553423 -
MBio Feb 2024Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems...
Many temperate phages encode prophage-expressed functions that interfere with superinfection of the host bacterium by external phages. phage P22 has four such systems that are expressed from the prophage in a lysogen that are encoded by the (repressor), , , and genes. Here we report that the P22-encoded SieA protein is necessary and sufficient for exclusion by the SieA system and that it is an inner membrane protein that blocks DNA injection by P22 and its relatives, but has no effect on infection by other tailed phage types. The P22 virion injects its DNA through the host cell membranes and periplasm via a conduit assembled from three "ejection proteins" after their release from the virion. Phage P22 mutants that overcome the SieA block were isolated, and they have amino acid changes in the C-terminal regions of the gene and encoded ejection proteins. Three different single-amino acid changes in these proteins are required to obtain nearly full resistance to SieA. Hybrid P22 phages that have phage HK620 ejection protein genes are also partially resistant to SieA. There are three sequence types of extant phage-encoded SieA proteins that are less than 30% identical to one another, yet comparison of two of these types found no differences in phage target specificity. Our data strongly suggest a model in which the inner membrane protein SieA interferes with the assembly or function of the periplasmic gp20 and membrane-bound gp16 DNA delivery conduit.IMPORTANCEThe ongoing evolutionary battle between bacteria and the viruses that infect them is a critical feature of bacterial ecology on Earth. Viruses can kill bacteria by infecting them. However, when their chromosomes are integrated into a bacterial genome as a prophage, viruses can also protect the host bacterium by expressing genes whose products defend against infection by other viruses. This defense property is called "superinfection exclusion." A significant fraction of bacteria harbor prophages that encode such protective systems, and there are many different molecular strategies by which superinfection exclusion is mediated. This report is the first to describe the mechanism by which bacteriophage P22 SieA superinfection exclusion protein protects its host bacterium from infection by other P22-like phages. The P22 prophage-encoded inner membrane SieA protein prevents infection by blocking transport of superinfecting phage DNA across the inner membrane during injection.
Topics: Humans; Bacteriophage P22; Superinfection; Bacteriophages; Prophages; Membrane Proteins; DNA; Amino Acids
PubMed: 38236051
DOI: 10.1128/mbio.02169-23