NK cells represent a cellular component of the mammalian innate immune system, and they mount rapid responses against viral infection, including the secretion of the potent antiviral effector cytokine IFN-γ. Following mouse CMV infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and with STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-γ production during mouse CMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-γ by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-γ secretion by NK cells during viral infection.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842983 | PMC |
| http://dx.doi.org/10.4049/jimmunol.2300402 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Harnessing Big Heterogeneous Data to Evaluate the Potential Impact of HIV Responses Among Key Populations in Sub-Saharan Africa: Protocol for the Boloka Data Repository Initiative.
JMIR Res Protoc
January 2025
Key Populations Program, Center for Public Health and Human Rights, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States.
Background: In South Africa, there is no centralized HIV surveillance system where key populations (KPs) data, including gay men and other men who have sex with men, female sex workers, transgender persons, people who use drugs, and incarcerated persons, are stored in South Africa despite being on higher risk of HIV acquisition and transmission than the general population. Data on KPs are being collected on a smaller scale by numerous stakeholders and managed in silos. There exists an opportunity to harness a variety of data, such as empirical, contextual, observational, and programmatic data, for evaluating the potential impact of HIV responses among KPs in South Africa.
View Article and Find Full Text PDFAssociation of poultry vaccination with interspecies transmission and molecular evolution of H5 subtype avian influenza virus.
Sci Adv
January 2025
State Key Laboratory of Remote Sensing Science, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Research Center for Respiratory Infectious Diseases, School of National Safety and Emergency Management, Center for Global Change and Public Health, Beijing Normal University, Beijing, China.
The effectiveness of poultry vaccination in preventing the transmission of highly pathogenic avian influenza viruses (AIVs) has been debated, and its impact on wild birds remains uncertain. Here, we reconstruct the movements of H5 subtype AIV lineages among vaccinated poultry, unvaccinated poultry, and wild birds, worldwide, from 1996 to 2023. We find that there is a time lag in viral transmission among different host populations and that movements from wild birds to unvaccinated poultry were more frequent than those from wild birds to vaccinated poultry.
View Article and Find Full Text PDFThe R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling.
PLoS Pathog
January 2025
State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood.
View Article and Find Full Text PDFSafety of two-dose schedule of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan) and heterologous additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised and immunocompetent individuals.
Rev Inst Med Trop Sao Paulo
January 2025
Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Divisão de Clínica de Moléstias Infecciosas e Parasitárias, Laboratório de Investigação Médica em Imunologia (LIM-48), SSão Paulo, São Paulo, Brazil.
Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group.
View Article and Find Full Text PDFSeasonal and periodic patterns in US COVID-19 mortality using the Variable Bandpass Periodic Block Bootstrap.
PLoS One
January 2025
Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, New York, United States of America.
Since the emergence of the SARS-CoV-2 virus, research into the existence, extent, and pattern of seasonality has been of the highest importance for public health preparation. This study uses a novel bandpass bootstrap approach called the Variable Bandpass Periodic Block Bootstrap to investigate the periodically correlated components including seasonality within US COVID-19 mortality. Bootstrapping to produce confidence intervals for periodic characteristics such as the seasonal mean requires preservation of the periodically correlated component's correlation structure during resampling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!