Phenotypic Characteristics of PD-1 and CTLA-4 Expression in Symptomatic Acute Hepatitis A

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.

Antitumor Effects of Genipin: New and Emerging Insights from Recent Studies

Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, there have been few literatures which review antitumor effects of genipin in a variety of in vitro/in vivo models of cancers yet. In this review, we present some of the latest findings in the studies of genipin focusing on antitumor effects and its mechanisms. In brief, genipin inhibits mitochondrial uncoupling protein 2 to increase accumulation of reactive oxygen species, leading to ROS/c-Jun N-terminal kinase-dependent apoptosis of cancer cells. Genipin also increase tissue inhibitors of metalloproteases (MMP), resulting to decrease activities of MMP-2 which plays a key role in metastasis of cancers. Genipin has shown a biphasic effects on cell death and survival in cancer cells as many other plant-derived phytochemicals do. Finally we discuss the potential of genipin as a promosing novel antitumor agent which could be applicable to chemotherapy and/or chemoprevention for cancers.

Current Trends in Studies of Epstein-Barr Virus (EBV) Associated Gastric Carcinoma

EBV infection has been causally associated with incidence of many carcinomas. EBV-associated gastric carcinoma (EBVaGC) has been classified as a unique gastric carcinoma subset, suggesting EBV infection is related to the development of gastric cancer. In this study, general trends of EBVaGC studies for last half-decades were reviewed in several perspectives of clinical significance, virological importance and etiological interests. Throughout this comprehensive reviewing, new study trends of EBV and EBVaGC for next half-decades were suggested.

The Applications of Hepatitis C Virus (HCV) Replication System in Developing Anti-HCV Reagents

Hepatitis C virus (HCV) is known to be a major cause of chronic hepatitis, liver cirrhosis and hepatocarcinoma. Therapeutic reagents are improving, but are still limited, and the protective vaccine against HCV is not available yet. However, the research of HCV life cycle and pathogenesis has been difficult due to obstacles, which are the lack of effective cell culture systems and small-animal models. Recently, breathtaking progress in terms of HCV replication system has been made using various forms of HCV clones and human hepatocarcinoma 7 cell lines (huh 7). The establishment of complete cell-culture system for HCV replication gave researchers opportunities to study the entire viral life cycle including entry, assembly, release of viral particles and the interaction with host cells. In fact, these efforts now appear to move into the identification and the development of innovative anti-HCV reagents. In this review, we go over the biological characters of HCV, a variety of in vitro cell culture, in vivo animal models of HCV infection, HCV immune-pathogenesis and the application of HCVcc system in terms of developing anti-HCV reagents.

Host Immune Responses Against Type A Influenza Viruses

The influenza viruses are divided into 3 different types, A, B and C, all of them are known as human pathogens. However, only type A influenza viruses cause both epidemic and pandemic influenza. Typically, influenza virus infects a respiratory tract, targets a lung and causes an acute infectious disease. Influenza infection can be identified by a high fever, headache, body ache and extreme fatigue. Host immune system against Influenza infection consists of innate immune response and adaptive immune response. Innate immune responses include recognition of influenza viruses by alveolar macrophages and natural killer cells. Adaptive immune responses contain influenza virus specific antibody production by B cells and killing infected cells by cytotoxic T cells. Initially, influenza viruses are recognized by pattern recognition receptors (PRRs) on respiratory epithelial cells and alveolar macrophages, which can induce efficient anti-viral immune responses. Host immune responses play crucial roles in defense against influenza virus infection but sometimes these may contribute to immuno-pathology, which results in serious tissue damage. In this review, we went over the understanding of current literature on subtypes of influenza A viruses, important viral antigens and anti-viral immune mechanisms.