Role of Lymphocytic Choriomeningitis Virus (LCMV) in Understanding Viral Immunology: Past,Present and Future

Lymphocytic choriomeningitis virus (LCMV) is a common infection of rodents first identified over eighty years ago in St. Louis, MO, U.S.A. It is best known for its application in immunological studies. The history of LCMV closely correlates with the development of modern immunology. With the use of LCMV as a model pathogen several key concepts have emerged: Major Histocompatibility Complex (MHC) restriction, T cell memory, persistent infections, T cell exhaustion and the key role of immune pathology in disease. Given the phenomenal infrastructure within this field (e.g., defined immunodominant and subdominant epitopes to all T cell receptor specificities as well as the cognate tetramers for enumeration in vivo) the study of LCMV remains an active and productive platform for biological research across the globe to this day. Here we present a historical primer that highlights several breakthroughs since the discovery of LCMV. Next, we highlight current research in the field and conclude with our predictions for future directions in the remarkable field of LCMV research.     

PGE_2,mPGES-1和HBx在肝细胞癌的表达及相关性

目的研究肝细胞癌（HCC）患者的前列腺素E2（PGE2）、微粒体型前列腺素E2合成酶-1（mPGES-1）与乙型肝炎病毒X蛋白（HBx）的表达情况、相关性和临床意义。方法采用酶联免疫法检测65例HCC患者外周血和癌组织的PGE2水平,用免疫组织化学法检测癌组织及癌旁肝组织mPGES-1和HBx的表达,并分析这些指标与患者的临床病理特征的关系。结果肝癌组织PGE2含量明显高于癌旁肝组织,分别为（9.10±2.03）ng/g和（2.78±0.19）ng/g;肝癌患者外周血中PGE2含量为（128.74±14.44）pg/ml,与肝癌组织中PGE2含量呈正相关（r=0.862）;HCC组织中HBx和mPGES-1的阳性表达率分别为86.2%和78.5%,而癌旁肝组织的HBx和mPGES-1阳性表达率分别为81.5%和46.2%,其中mPGES-1蛋白在肝癌组织及癌旁肝组织的阳性表达率差异有统计学意义（P〈0.05）。HBx和mPGES-1的表达升高与肝癌分化程度和肝外是否转移相关（P〈0.05）;HBx的表达与mPGES-1的表达呈正相关（r=0.389）;外周血PGE2水平和组织mPGES-1的表达呈正相关（r=0.526）。结论肝细胞癌与PGE2、HBx、mPGES-1表达相关;可以通过检测肝细胞癌患者外周血的PGE2水平来辅助评估肝癌的复发转移;HBx和mPGES-1可作为肝癌的治疗靶点进行更深入的研究。     

Interactions between metabolic disorders (diabetes, gallstones, and dyslipidaemial and the progression of chronic hepatitis C virus infection to cirrhosis and hepatocellular carcinoma. A cross-sectional multicentre survey

BACKGROUND: Diabetes, gallstones and dyslipidaemia are widespread, metabolically related, disorders that can affect the liver, often in a clinically silent fashion. AIM: To investigate whether the presence of these disorders may worsen chronic viral disease by inducing additional liver damage, revealed by variations in serum increases of aminotransferase, alkaline phosphatase and gamma-glutamyl-transpeptidase activities. PATIENTS AND METHODS: This retrospective, cross-sectional study involved 1,195 patients with chronic hepatitis C virus infection: 47.2% chronic hepatitis, 45.2% cirrhosis, and 7.6% hepatocellular carcinoma. 14.9% of patients had enzymatic cholestasis, defined as combined increase of alkaline phosphatase and gamma-glutamyl-transpeptidase. A Log-linear statistical model was applied to the following variables: stages of liver disease, diabetes, cholelithiasis, hypertriglyceridaemia, hypercholesterolaemia, and enzymatic cholestasis. RESULTS: Log-linear analysis, applied to categorical variables, revealed, for the first time, a three-way interaction between the stages of chronic liver disease, diabetes, and enzymatic cholestasis. Two-way interactions demonstrated that liver disease stages correlated directly to the prevalence of cholelithiasis and inversely to hypercholesterolaemia. Irrespective of the liver disease stage, hypertriglyceridaemia correlated to hypercholesterolaemia. CONCLUSIONS: This study discloses a synergistic liver damaging effect of diabetes and hepatitis C virus. The three-way interaction obtained by our analysis suggests that diabetes is a risk factor for the progression of viral liver disease and that it contributes to disease evolution, at least in part, by induction of cholestasis.