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Nature Communications Jun 2024During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the...
During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.
Topics: Humans; Interferon-gamma; Cell Adhesion; T-Lymphocytes; Intercellular Adhesion Molecule-1; Keratinocytes; Herpesvirus 3, Human; Varicella Zoster Virus Infection; Leukocytes, Mononuclear; Viral Envelope Proteins; Lymphocyte Function-Associated Antigen-1
PubMed: 38909022
DOI: 10.1038/s41467-024-49657-4 -
Phytomedicine : International Journal... Apr 2024Illness resulting from influenza is a global health problem that has significant adverse socioeconomic impact. Although various strategies such as flu vaccination have...
BACKGROUND
Illness resulting from influenza is a global health problem that has significant adverse socioeconomic impact. Although various strategies such as flu vaccination have beneficial effects, the risk of this illness has not been eliminated. The use of botanicals may provide a complementary approach by enhancement of the host antiviral immune response.
PURPOSE
Generate preclinical data using rodent models to determine the most effective utility of a Limnospira (formerly Arthrospira)-derived oral supplement (Immulina®) for enhancing host immunity to improve antiviral resilience.
STUDY DESIGN
Two non-lethal mouse models (prophylactic and therapeutic) were used to evaluate the impact of Immulina® on increasing host resilience against experimental influenza infection.
METHODS
Mice were fed Immulina® only for the 2 weeks prior to viral infection (prophylactic regime) or starting 3 days post-viral infection (at the onset of symptoms, therapeutic design). Three doses of Immulina® were evaluated in each model using both female and male mice.
RESULTS
Significant protective effect of Immulina® against viral illness was observed in the prophylactic model (improved clinical scores, less body weight loss, decreased lung/body weight ratio, lower lung viral load, and increased lung IFN-γ and IL-6). Substantially less (minimal) protective effect was observed in the therapeutic model.
CONCLUSION
This study demonstrates that Immulina® exerts a protective effect against influenza illness when administered using a prophylactic regime and may not be effective if given after the onset of symptoms. The results will help to optimally design future clinical trials.
PubMed: 38908194
DOI: 10.1016/j.phymed.2024.155588 -
International Immunopharmacology Jun 2024Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea...
Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection.
PubMed: 38908077
DOI: 10.1016/j.intimp.2024.112428 -
Polish Journal of Microbiology Jun 2024Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors,...
Interferon-alpha (IFN-α) is a first-line drug for treating chronic hepatitis B (CHB). Guanylate-binding protein 1 (GBP1) is one of the interferon-stimulating factors, which participates in the innate immunity of the host and plays an antiviral and antibacterial role. In this study, we explored how GBP1 is involved in IFN-α antiviral activity against HBV. Before being gathered, HepG2-NTCP and HepG2 2.15 cells were transfected with the wild-type hGBP1 plasmid or si-GBP1, respectively, and followed by stimulation with Peg-IFNα-2b. We systematically explored the role of GBP1 in regulating HBV infection in cell models. Additionally, we also examined GBP1 levels in CHB patients. GBP1 activity increased, and its half-life was prolonged after HBV infection. Overexpression of GBP1 inhibited the production of HBsAg and HBeAg, as well as HBs protein and HBV total RNA levels, whereas silencing of GBP1 inhibited its ability to block viral infections. Interestingly, overexpressing GBP1 co-treatment with Peg-IFNα-2b further increased the antiviral effect of IFN-α, while GBP1 silencing co-treatment with Peg-IFNα-2b partly restored its inhibitory effect on HBV. Mechanistically, GBP1 mediates the anti-HBV response of Peg-IFNα-2b by targeting HBs. Analysis of clinical samples revealed that GBP1 was elevated in CHB patients and increased with Peg-IFNα-2b treatment, while GBP1 showed good stability in the interferon response group. Our study demonstrates that GBP1 inhibits HBV replication and promotes HBsAg clearance. It is possible to achieve antiviral effects through the regulation of IFN-α induced immune responses in response to HBV.
Topics: Humans; Interferon-alpha; Hepatitis B virus; Antiviral Agents; GTP-Binding Proteins; Hep G2 Cells; Hepatitis B, Chronic; Male; Hepatitis B Surface Antigens; Female; Adult; Virus Replication; Hepatitis B
PubMed: 38905278
DOI: 10.33073/pjm-2024-021 -
Frontiers in Microbiology 2024has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown...
has been used extensively for dissecting the genetic and functional bases of host innate antiviral immunity and virus-induced pathology. Previous studies have shown that the presence of endosymbionts in confers resistance to infection by certain viral pathogens. Zika virus is an important vector-borne pathogen that has recently expanded its range due to the wide geographical distribution of the mosquito vector. Here, we describe the effect of on the immune response of adult flies following Zika virus infection. First, we show that the presence of endosymbionts promotes the longevity of uninfected wild type adults and increases the survival response of flies following Zika virus injection. We find that the latter effect is more pronounced in females rather than in males. Then, we show that the presence of regulates Zika virus replication during Zika virus infection of female flies. In addition, we demonstrate that the antimicrobial peptide-encoding gene and the sole Jun N-terminal kinase-specific MAPK phosphatase are upregulated in female adult flies, whereas the immune and stress response gene is upregulated in male individuals. Finally, we find that the activity of RNA interference and Toll signaling remain unaffected in Zika virus-infected female and male adults containing compared to flies lacking the endosymbionts. Our results reveal that endosymbionts in affect innate immune signaling activity in a sex-specific manner, which in turn influences host resistance to Zika virus infection. This information contributes to a better understanding of the complex interrelationship between insects, their endosymbiotic bacteria, and viral infection. Interpreting these processes will help us design more effective approaches for controlling insect vectors of infectious disease.
PubMed: 38903791
DOI: 10.3389/fmicb.2024.1380647 -
Frontiers in Immunology 2024The mitochondrial anti-viral signaling (MAVS) protein is an intermediary adaptor protein of retinoic acid-inducible gene-1 (RIG-I) like receptor (RLR) signaling, which...
MAVS disruption impairs downstream signaling and results in higher virus replication levels of salmonid alphavirus subtype 3 but not infectious pancreatic necrosis virus .
The mitochondrial anti-viral signaling (MAVS) protein is an intermediary adaptor protein of retinoic acid-inducible gene-1 (RIG-I) like receptor (RLR) signaling, which activates the transcription factor interferon (IFN) regulatory factor 3 (IRF3) and NF-kB to produce type I IFNs. MAVS expression has been reported in different fish species, but few studies have shown its functional role in anti-viral responses to fish viruses. In this study, we used the transcription activator-like effector nuclease (TALEN) as a gene editing tool to disrupt the function of MAVS in Chinook salmon () embryonic cells (CHSE) to understand its role in induction of interferon I responses to infections with the (+) RNA virus salmonid alphavirus subtype 3 (SAV-3), and the dsRNA virus infectious pancreatic necrosis virus (IPNV) infection. A MAVS-disrupted CHSE clone with a 7-aa polypeptide (GVFVSRV) deletion mutation at the N-terminal of the CARD domain infected with SAV-3 resulted in significantly lower expression of IRF3, IFNa, and ISGs and increased viral titer (1.5 log) compared to wild-type. In contrast, the IPNV titer in MAVS-disrupted cells was not different from the wild-type. Furthermore, overexpression of salmon MAVS in MAVS-disrupted CHSE cells rescued the impaired type I IFN-mediated anti-viral effect against SAV-3.
Topics: Animals; Infectious pancreatic necrosis virus; Alphavirus; Virus Replication; Signal Transduction; Adaptor Proteins, Signal Transducing; Fish Diseases; Alphavirus Infections; Salmon; Fish Proteins; Interferon Regulatory Factor-3; Birnaviridae Infections
PubMed: 38903507
DOI: 10.3389/fimmu.2024.1401086 -
Cureus May 2024This study aimed to investigate the referral rates of oral lichen planus (OLP) and untreated hepatitis virus-infected patients by dentists to hepatologists.
OBJECTIVES
This study aimed to investigate the referral rates of oral lichen planus (OLP) and untreated hepatitis virus-infected patients by dentists to hepatologists.
MATERIALS AND METHODS
The study was conducted at three dental clinics in the Oita prefecture between November 2021 and June 2023. Two distinct groups of patients who visited the dentist for dental treatment were included: those with liver disease and concurrent hepatitis C virus (HCV) or hepatitis B virus (HBV) infection and those diagnosed with OLP. The rate of medical referrals to a hepatologist was investigated. Data on the number of patients, gender, age, diagnosis of liver disease, and referral practices were collected from the records submitted by each dental clinic. Information about the HCV and HBV infection status was collected through interviews with the dentists.
RESULTS
A total of 1,665 patients were included, of which 10 were HCV-infected, five were HBV-infected, and six were diagnosed with OLP. None of the 15 patients with liver disease were referred to a hepatologist by their dentists. Nine out of the 10 HCV-infected patients had achieved sustained virological response (SVR) after antiviral treatment. Of the six patients with OLP, one had a history of HBV infection, one had severe fatty liver, and the remaining four had normal livers; five of the OLP patients were referred to a hepatologist (83.3%).
CONCLUSION
A high referral rate from dentists to hepatologists was observed among the OLP patients. However, the study highlighted the difficulties in identifying hepatitis patients and establishing appropriate medical coordination in dental institutions.
PubMed: 38903276
DOI: 10.7759/cureus.60624 -
AIDS Research and Therapy Jun 2024The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030,...
INTRODUCTION
The World Health Organisation has implemented multiple HIV prevention policies and strived to achieve the 90-90-90 goal by 2020, achieving the 95-95-95 goal by 2030, which refers to 95% of patients living with HIV knowing their HIV status, 95% of patients living with HIV receiving continual care and medication, and 95% of patients living with HIV exhibiting viral suppression. However, how to measure the status of viral suppression varies, and it is hard to indicate the quality of HIV care. The study aimed to examine the long-term viral load suppression in these cases and explore potential factors affecting the control of long-term viral load.
METHODS
This study analyzed viral load testing data from HIV patients who are still alive during the period from notification up to 2019-2020. Three indicators were calculated, including durable viral suppression, Viremia copy-years, and Viral load > 1,500 copies/ml, to assess the differences between them.
RESULTS
Among the 27,706 cases included in the study, the proportion of persistent viral load suppression was 87%, with 4% having viral loads exceeding 1,500 copies/ml. The average duration from notification to viral load suppression was 154 days, and the geometric mean of annual viral replication was 90 copies*years/ml. Regarding the last available viral load measurement, 96% of cases had an undetectable viral load. However, we observed that 9.3% of cases, while having an undetectable viral load for their last measurement, did not show consistent long-term viral load suppression. An analysis of factors associated with non-persistent viral load suppression revealed higher risk in younger age groups, individuals with an educational level of high school or below, injection drug users, cases from the eastern region, those seeking care at regional hospitals, cases with drug resistance data, individuals with lower healthcare continuity, and those with an initial CD4 count below 350 during the study period.
CONCLUSIONS
The recommendation is to combine it with the indicator of sustained viral load suppression for a more accurate assessment of the risk of HIV transmission within the infected community.
Topics: Humans; Viral Load; HIV Infections; Male; Female; Adult; Taiwan; Middle Aged; Anti-HIV Agents; Young Adult; Aged; Adolescent; HIV-1; Sustained Virologic Response
PubMed: 38902777
DOI: 10.1186/s12981-024-00626-3 -
BMC Infectious Diseases Jun 2024Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral...
BACKGROUND
Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19.
METHODS
For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology.
FINDINGS
CD4 T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033).
INTERPRETATION
Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.
Topics: Humans; COVID-19; SARS-CoV-2; Male; Female; Middle Aged; CD4-Positive T-Lymphocytes; Severity of Illness Index; Adult; Immunity, Cellular; Inflammation; Aged; Viral Load; Interferon-gamma; Lymphocyte Activation; Leukocytes, Mononuclear
PubMed: 38902613
DOI: 10.1186/s12879-024-09490-y -
NPJ Vaccines Jun 2024The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were...
The ChAdOx1 nCoV-19 (COVISHIELD) vaccine has emerged as a pivotal tool in the global fight against the COVID-19 pandemic. In our previous study eligible subjects were supplemented with calcifediol, a direct precursor to the biologically active form of vitamin D, calcitriol with an objective to enhance the immunogenicity of the COVISHIELD vaccine. Herein we investigated the effects of calcifediol supplementation on gene expression profiles in individuals who received the COVISHIELD vaccine. Peripheral blood mononuclear cells were isolated from vaccinated individuals with and without calcifediol supplementation at baseline, 3rd and 6th month, and the gene expression profiles were analyzed using high-throughput sequencing. The results revealed distinct patterns of gene expression associated with calcifediol supplementation, suggesting potential molecular mechanisms underlying the beneficial effects of calcifediol in improving the efficacy of COVISHIELD vaccine via augmentation of T cell activation, proliferation and T cell memory responses. Additionally, there was upregulation of NOD like receptor, JAK/STAT and TGF beta signaling pathways. Calcifediol supplementation in vaccinated individuals also downregulated the pathways related to the Coronavirus disease. Taken together, our findings provide valuable insights into the interplay between vitamin D receptor (VDR) signaling and vaccine-induced immune responses and offer another approach in improving vaccination induced antiviral responses.
PubMed: 38902265
DOI: 10.1038/s41541-024-00909-w