T11TS immunotherapy augments microglial and lymphocyte protective immune responses against Cryptococcus neoformans in the brain.

Cryptococcus neoformans, the encapsulated yeast acquired through inhalation, remains localized in lungs, but harbours the CNS in immunocompromised individuals. Several treatment regimes have failed combating this disease totally, but long-term usage of drugs leads to organ damage. As T11-target structure (T11TS) has documented profound immune potentiation, we aimed to investigate the role of microglia, pivotal immune cells of brain in ameliorating cryptococcosis, with T11TS immunotherapy. Murine model with C neoformans infection was prepared by intraperitoneal injection and the brains of rats examined 7 days post-infections for histopathology by PAS and Alcian blue staining corroborated with organ fungal burden evidencing restorative T11TS action on Cryptococcal meningitis. Immunotherapy with three doses of T11TS, a CD2 ligand, in C neoformans infected rats, upregulates toll-like receptors 2, -4 and -9 of microglia, indicating increased phagocytosis of the fungus. Flowcytometric analysis revealed increased numbers of T11TS treated brain infiltrating CD4+ and CD8+ T-lymphocytes along with increased MHC I and MHC II on microglia, activating the infiltrating lymphocytes aiding the killing mechanism. Present study also indicated that T11TS increased production of Th1 inflammatory cytokines conducive to fungal elimination while the inhibitory Th2 cytokines were dampened. This preclinical study is first of its kind to show that T11TS effected profound immune stimulation of microglial activity of C neoformans infected rats eradicating residual fungal burden from the brain and can be a useful therapeutic strategy in fighting against this deadly disease.

Correlation of serum HCV core concentration with blood level of lipid and antioxidants in various forms of liver diseases.

BACKGROUND/AIMS: The present study was designed to investigate the effect of hepatitis C virus (HCV) core protein expression on the blood level of lipids, lipoproteins and apolipoprotein in various forms of liver diseases. At the same time, effect of HCV core protein was also studied on the level of antioxidants in these patient groups. The aim behind this study was to explore the possibility of HCV core induced lipid changes and ensuing oxidative liver damage in these liver diseases. METHODOLOGY: We studied a total number of 130 patients including 50 patients with acute viral hepatitis (AVH), 30 with chronic hepatitis (CH), 30 with hepatic cirrhosis and 20 patients with fulminant hepatic failure (FHF). Sera from all these patients were analyzed for hepatitis viral markers and HCV core protein using EIA assays. Sera/plasma from them were simultaneously analyzed for total cholesterol, triglyceride, low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A-1 and B, and also for antioxidants. RESULTS: Analysis of data demonstrated the presence of viral hepatitis B, C and E infections in these cases. Hepatitis A and D infections were absent in all the patients. When data on lipid and lipoprotein were analyzed in relation to HCV core expression, we could not observe a significant change in the serum level of total cholesterol, triglyceride, LDL, HDL, apolipoprotein A-1 and apoprotein B in core positive patients as compared to core negative cases. However, lipoprotein (a) [Lp(a)] level was significantly reduced in core positive patients as compared to core negative cases. Furthermore, analysis of Superoxide dismutase (SOD), Total antioxidant (TAO) and Uric Acid in these patients demonstrated only a minor change in SOD and TAO levels in relation to HCV core, though at the same time, Uric Acid was found raised in all the groups. CONCLUSIONS: These observations clearly indicate that core expression does not bring a significant change in serum level of lipids, lipoprotein and apoproteins. Similarly, HCV core expression also does not show a major change in SOD and TAO levels suggesting an insignificant impact of core on oxidative stress during liver diseases.

Significance of hepatitis C virus core protein in the diagnosis of hepatitis C virus infection in different liver diseases.

The present article describes the presence of hepatitis C virus (HCV) core protein in relation to HCV antibody in different types of liver diseases caused by hepatitis viral infections. One hundred thirty patients with various types of liver diseases, including those with acute viral hepatitis (n = 50), chronic viral hepatitis (n = 30), cirrhosis of the liver (n = 30), and fulminant hepatic failure (n = 20), were analyzed for HCV core protein, HCV-ribonucleic acid (RNA) and anti-HCV antibodies using enzyme immunoassays and reverse transcriptase-polymerase chain reaction. All patients were also simultaneously analyzed for other hepatitis markers to diagnose hepatitis A to E in all cases. Patients with HCV infection were additionally tested for HCV core protein and HCV-RNA. The results of analysis demonstrated the presence of hepatitis B, C, and E in different proportions of patients with these liver diseases. Hepatitis A and D infections were absent in all cases. Analysis of sera from acute viral hepatitis demonstrated the presence of HCV core protein, HCV-RNA, anti-HCV antibodies, and both core protein and anti-HCV together in 18%, 16%, 6%, and 2% of cases, respectively. In fulminant hepatic failure patients, these markers were recorded in 20%, 10%, 10%, and 5% of cases, respectively. In the chronic viral hepatitis group, the pattern was reversed, and their presence was recorded in 13.3%, 13.3%, 46.6%, and 10% of cases, respectively. Similarly, in cirrhosis patients, these markers were noted in 23.3%, 23.3%, 23.3%, and 13.3% of cases, respectively. None of the control sera were positive for any hepatitis marker. The significance of HCV core protein in relation to HCV-RNA and anti-HCV for the diagnosis of HCV infection in different liver diseases has been discussed.

Hepatitis C virus core protein: an update on its molecular biology, cellular functions and clinical implications.

The present review article is an update on various features of hepatitis C virus (HCV) core protein including its molecular biology, role in HCV replication, involvement in HCV pathogenesis, etiological role in hepatocellular carcinogenesis, significance in diagnosis and vaccination against HCV infection. Core protein is a structural protein of HCV virus and has only recently been characterized. It was found to play a major role in HCV-induced viral hepatitis. Although published information shows a lot about the clinical significance of HCV core protein, several studies are still needed to demonstrate its exact significance in viral biology and underlying HCV pathogenesis.