National Institute of Allergy and Infectious Diseases

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis

Abstract Background Differential expression analysis is a central tool for studying the biological processes altered in human diseases via transcriptomic signatures. However, transcriptomic datasets are systematically confounded by latent variables from two distinct sources: unme...

Knock-Out of Prion Protein Associated with Reactivity and Mitochondrial Abnormalities in a Novel Human Astrocyte Model

Human prion diseases are fatal neurodegenerative diseases caused by misfolding and aggregation of the cellular prion protein, PrP. Current therapeutic avenues focus on the removal of PrP to decrease its availability in the brain. Numerous studies have investigated the role of neu...

MATRIN3 deficiency in human cells triggers an autoinflammatory response via cGAS–STING activation

MATRIN3 (MATR3) is a broadly expressed nuclear RNA-binding protein. However, the mechanisms by which MATR3 maintains human cellular health remain poorly understood. In this study, we employed gene editing to model MATR3 deficiency in human induced pluripotent stem cells (iPSCs) a...

Corticosteroids drive oral candidiasis by impairing type-17 immunity without inducing interferon-gammopathy

ABSTRACT Oral candidiasis arises from either genetic immune defects or iatrogenic immune suppression, most commonly due to corticosteroid therapy. Although the cortisone acetate mouse model is widely used to study corticosteroid-associated oral candidiasis, the underlying mechani...

Endogenous anti-Ebola virus GP 1,2 antibodies interfere with detection of secreted glycoprotein in the blood of EVD patients

ABSTRACT Ebola disease (EBOD) is a highly infectious disease with severe hemorrhagic symptoms. It is caused by orthoebolaviruses , which include the Ebola virus ( Orthoebolavirus zairense ) (EBOV) causing Ebola virus disease (EVD), the most lethal EBOD to humans. Through co-trans...

Pharmacokinetics of Efavirenz in Pregnancy and Postpartum with and Without First-line Tuberculosis Drugs: Results from IMPAACT P1026s

Efavirenz (EFV) pharmacokinetics (PK) may be influenced by both pregnancy-related physiological changes and concurrent treatment for drug-sensitive tuberculosis (DS-TB), and intensive 24-h EFV PK data during rifampin (RIF)/ isoniazid (INH) treatment in pregnant women living with...

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the...

A Live Single-Cycle RSV Vaccine with Immune Responses Focused on Prefusion F and the Central Conserved Region of Attachment Protein G

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease in infants and children, and a pediatric vaccine is not available. Among various approaches, live vaccines are attractive as they induce broad multi-antigenic responses and have never bee...

Oral Fungal Infection Impacts Epithelial Innate Immunity to Promote Local and Distal Squamous Cell Carcinoma Progression

Abstract Fungi have been detected within human tumors and shown to support tumor progression. A better understanding of how intratumoral fungi evade innate immunity, remodel the tumor microenvironment (TME), and promote tumorigenesis may provide insights into cancer pathogenesis...

Zebrafish larvae swim bladder serves as a model to study Mycobacterium abscessus infection kinetics, host–pathogen interactions and drug efficacy

Mycobacterium abscessus , a nontuberculous mycobacterium (NTM), is a cause of chronic lung infection primarily affecting people with underlying conditions such as cystic fibrosis and other causes of bronchiectasis. Mostly caudal vein infection of zebrafish embryos has been used f...

Molecular epidemiology and management of non-tuberculous mycobacteria isolated from patients in Ukraine, 2022–2024

Non-tuberculous mycobacteria (NTM) are increasingly recognized worldwide as significant causes of chronic pulmonary disease, particularly among individuals with underlying structural lung disorders or immunosuppression. However, data on the epidemiology and clinical management of...

Human-inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity

Abstract We previously reported inherited RORγT deficiency in seven patients from three ancestries (Chilean, Palestinian, Saudi Arabian) with mycobacterial disease and chronic mucocutaneous candidiasis (CMC). We report here five additional patients from different ancestries (Afgh...

Measurement of binding antibodies to SARS-CoV-2 variants elicited by natural infection and COVID-19 vaccines in a sub-Saharan African population

Abstract Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly with respect to antibody (Ab) binding across SARS-CoV-2 variants and for different types of vaccine platforms. We assessed anti-spike (anti-S) antibody binding to nin...

Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis From Uganda

Abstract Objective Severe tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature o...

Distinctive properties of the prion protein in the brain and retina in the amyloidosis associated with the PRNP F198S mutation

Abstract Prion protein (PrP) deposits in the form of diffuse and cored plaques occur in most gray matter areas of the brain of individuals affected by Gerstmann-Sträussler-Scheinker disease (GSS) associated with the F198S mutation in PRNP; however, the PrP deposits in the retina...

VIProDesign: viral protein panel design for highly variable viruses to evaluate immune responses and identify broadly neutralizing antibodies

Motivation: Highly mutable viruses continuously evolve, with some posing major pandemic risks. However, standardized neutralization assays and up-to-date viral panels are often lacking, limiting evaluation of immunogens and identification of broadly neutralizing antibodies. Closi...

The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy

In individuals on effective antiretroviral therapy, integrated HIV proviruses persist within CD4 T cells, forming a viral reservoir that rebounds if treatment is stopped. Identifying and targeting these rare, infected cells is critical for advancing therapies, but methods to stud...

Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8+ T cell-macrophage interactions.

T cell infiltration and reduces T cell activation and proliferation; and iii) therapeutic strategies, including D-1MT, that improve intragranulomatous killing hold strong translational potential.

Potent type-specific de novo antibodies complement broadly reactive imprinted antibodies in immune responses to SARS-CoV-2 variants

Abstract For rapidly mutating viruses such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune memory recalled by antigenically drifted variants primarily comprises antibodies that cross-react to the priming strain rather than de novo eli...

Changes in neurodevelopmental outcomes from 24 to 36 months among children HIV-exposed uninfected (CHEU) and HIV-unexposed (CHU)

Objective: To compare neurodevelopment through 36 months between breastfed children who are HIV-exposed and uninfected (CHEU) exposed to maternal dolutegravir (DTG)-based antiretroviral therapy (ART) and children born to mothers without HIV (CHU). Methods: We enrolled a prospecti...