Epstein-Barr virus hijacks B cell metabolism to establish persistent infection and drive pathogenesis.

When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein-Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host's lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation.

Syphilis Reactivates Latent Epstein-Barr Virus Reservoir via Toll-Like Receptor 2 and B-Cell Receptor Activation.

Latent Epstein-Barr virus (EBV) infection can clinically reactivate in immunosuppressed individuals causing lymphoproliferative disease and rarely hepatitis. In this study, we provide in vivo and in vitro evidence that infection can cause EBV reactivation with hepatitis in an immunocompetent patient. We report the diagnostic challenges and immunological findings of coinciding syphilis and EBV-associated hepatitis.

SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1-Nrf2.

Whether screening the metabolic activity of immune cells facilitates discovery of molecular pathology remains unknown. Here we prospectively screened the extracellular acidification rate as a measure of glycolysis and the oxygen consumption rate as a measure of mitochondrial respiration in B cells from patients with primary antibody deficiency. The highest oxygen consumption rate values were detected in three study participants with persistent polyclonal B cell lymphocytosis (PPBL).

CD56-negative NK cells with impaired effector function expand in CMV and EBV co-infected healthy donors with age.

Natural killer cells lacking expression of CD56 (CD56 NK cells) have been described in chronic HIV and hepatitis C virus infection. Features and functions of CD56 NK cells in the context of latent infection with CMV and / or EBV with age are not known. In a cohort of healthy donors >60 years of age, we found that co-infection with CMV and EBV drives expansion of CD56 NK cells.

A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging.

Mitogen-activated protein kinases (MAPKs) including Erk, Jnk and p38 regulate diverse cellular functions and are thought to be controlled by independent upstream activation cascades. Here we show that the sestrins bind to and coordinate simultaneous Erk, Jnk and p38 MAPK activation in T lymphocytes within a new immune-inhibitory complex (sestrin-MAPK activation complex (sMAC)). Whereas sestrin ablation resulted in broad reconstitution of immune function in stressed T cells, inhibition of individual MAPKs allowed only partial functional recovery.

Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5'-Monophosphate-Activated Protein Kinase.

NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals.