The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies.

Purpose Of Review: Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance.

Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency.

Background: Common Variable Immunodeficiency (CVID) is classified as a 'Predominantly Antibody Deficiency' (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with cytomegalovirus (CMV) infection, a hallmark of 'combined immunodeficiency'. CMV infection also has the potential to drive immune dysregulation contributing to significant morbidity and mortality in CVID.

The role of MKK4 in T-cell development and immunity to viral infections.

The stress-activated protein kinases (SAPKs)/c-Jun-N-terminal-kinases (JNK) are members of the mitogen-activated protein kinase family. These kinases are responsible for transducing cellular signals through a phosphorylation-dependent signaling cascade. JNK activation in immune cells can lead to a range of critical cellular responses that include proliferation, differentiation and apoptosis.

Speculations on the evolution of humoral adaptive immunity.

The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers.

Multiplexed Division Tracking Dyes for Proliferation-Based Clonal Lineage Tracing.

The generation of cellular heterogeneity is an essential feature of immune responses. Understanding the heritability and asymmetry of phenotypic changes throughout this process requires determination of clonal-level contributions to fate selection. Evaluating intraclonal and interclonal heterogeneity and the influence of distinct fate determinants in large numbers of cell lineages, however, is usually laborious, requiring familial tracing and fate mapping.

The regulation of lymphocyte activation and proliferation.

Activation induced proliferation and clonal expansion of antigen specific lymphocytes is a hallmark of the adaptive immune response to pathogens. Recent studies identify two distinct control phases. In the first T and B lymphocytes integrate antigen and additional costimuli to motivate a programmed proliferative burst that ceases with a return to cell quiescence and eventual death.