A telomerase-derived peptide regulates reactive oxygen species and hepatitis C virus RNA replication in HCV-infected cells via heat shock protein 90.

GV1001, a synthetic peptide derived from human telomerase, has a range of diverse biological activities, including an antioxidant function. Here, we investigated the role of GV1001 in hepatitis C virus (HCV)-infected Huh7.5 (JFH-1) cells. We showed that GV1001 inhibited the production of ROS with decreased MAP kinase signaling. Interestingly, GV1001 lost its antioxidant activity as ROS levels decreased, resulting in a reduction in extracellular heat shock protein 90 (eHSP90) as low-density lipoprotein receptor-related protein 1 (LRP1) was blocked or knocked-down. GV1001 binds to eHSP90 and is delivered into the cell by endocytosis via LRP1. Endocytosed GV1001 finally suppressed ROS generation, presumably by hindering the interaction between eHSP90 and NADPH oxidase (NOX). Importantly, GV1001 suppressed HCV RNA replication in JFH-1 cells by inhibiting the binding of HSP90 to FKBP8, a member of the FK506-binding protein family. We also found that HSP90 expression was high in HCV-infected hepatocytes. Therefore, our data suggest that GV1001 may be a good therapeutic agent by controlling HCV RNA replication, as well as by preferentially targeting cells under conditions of oxidative stress.

Peripheral immature B cells: modulators of autoimmunity.

B cells play an essential role in humoral immunity by producing antigen-specific antibodies. However, B cells also participate in cellular immune responses by presenting antigens, providing costimulation, and producing cytokines to activate and expand effectors and memory T cell populations. Recent identification of antibody-independent functions of B cells has reawakened interest in the many roles of B cells in normal immune responses as well as in autoimmune diseases. B cells interact with other immunocompetent cells during a tightly regulated immune activation process, acting as both effector and regulator. If this balance between effector and regulatory B cell functions is disrupted, harmful effects of immune activation such as autoimmunity can occur. In this review, we will discuss the role of human peripheral immature B cells in normal immune responses as a modulator of autoimmunity. We will also discuss abnormalities of these cells in pathogenesis of systemic autoimmunity with particular focus on systemic lupus erythematosus pathogenesis.