Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections.

Protein kinases (PKs) are enzymes that catalyze the transfer of the terminal phosphate group from ATP to a protein acceptor, mainly to serine, threonine, and tyrosine residues. PK catalyzed phosphorylation is critical to the regulation of cellular signaling pathways that affect crucial cell processes, such as growth, differentiation, and metabolism. PKs represent attractive targets for drugs against a wide spectrum of diseases, including viral infections. Two different approaches are being applied in the search for antivirals: compounds directed against viral targets (direct-acting antivirals, DAAs), or against cellular components essential for the viral life cycle (host-directed antivirals, HDAs). One of the main drawbacks of DAAs is the rapid emergence of drug-resistant viruses. In contrast, HDAs present a higher barrier to resistance development. This work reviews the use of chemicals that target cellular PKs as HDAs against virus of the Flaviviridae family (Flavivirus and Hepacivirus), thus being potentially valuable therapeutic targets in the control of these pathogens.

Hepatitis G virus infection in multitransfused Egyptian children.

The purpose of this study was to identify the magnitude of the hepatitis G virus infection in 33 multitransfused cases and 20 matched controls. All were tested for liver biochemical profile, HBsAg, HCV-antibody, HGV-RNA, and antibody to envelop protein E(2). HGV was detected alone in 61% of the multitransfused cases and 15% of the controls. Hepatitis markers were negative in 21% of cases versus 70% of controls. HGV envelope antibody was detected in 12% of cases, and none of controls. Mean values of transaminases in HGV positives and negatives showed no significant differences. HGV infection is highly prevalent in Egyptian children with no impact in infected cases.

[GB virus C: lack of association with transaminases levels, CD4 and HIV viral load in aids patients]. / Virus GB-C: ausencia de asociación con niveles de transaminasas, CD4 y carga vírica en pacientes con sida.

OBJECTIVE: To study the prevalence of GBV-C-RNA in sera of HIV-infected patients and determine whether differences in immunological condition and hepatic disease exist between GBV-C positive and negative patients. METHODS: The presence of GBV-C-RNA was determined in sera of 222 HIV-positive patients by semi-automated RT-PCR. A comparison of GBV-C-RNA positive and negative patients was made by studying a series of clinical and analytical parameters. This same comparison was made in particular between those coinfected with HCV and GBV-C and those who only presented GBV-C. RESULTS: Prevalence of GBV-C-RNA was 28.8%. The most frequent hepatotropic virus was HCV, appearing in 71.6% of cases. Coinfection with HCV and HGV was present in 17% and 8.6% only had GBV-C. Patients positive for GBV-C-RNA showed clinical and analytical characteristics similar to those found in GBV-C-RNA negative patients. Among the HCV-GBV-C coinfected and those presenting HGV as the only virus it was observed that the coinfected group presented alterations in transaminases and predominance of parenteral transmission as a risk factor for HIV, whereas the GBV-C group presented normal transaminases and predominance of sexual transmission. No differences were perceived in mean CD4 and HIV-RNA values in both groups. CONCLUSIONS: Being positive for GBV-C in HIV-positive patients does not influence the presence of hepatic disease that in these patients is frequently accompanied by coinfection with other hepatotropic viruses. Moreover, it does not seem to influence the viremia of the HIV nor the CD4 cell counts.

[The clinical and enzymatic changes in patients with viral hepatitis G infection].

For the purpose of making sure the clinical significance of hepatitis G virus, RT-nested PCR was applied to detect HGV RNA in 165 hepatitis patients, which included 24 acute hepatitis, 78 chronic hepatitis, 18 hepatitic cirrhosis, 4 hepatocellularcarcinom and 41 HBV and HCV carriers. The results showed that the infection of HGV existed in all kinds of hepatitis patients. Among the acute hepatitis 12.5% (3/24) was HGV RNA positive. 19 (24.4%) cases were HGV RNA positive in chronic hepatitis, among which 4 cases were simply HGV RNA positive (5.13%). The serum ALT level in 3 cases of simple acute HGV patients was between 488 +/- 65 U/L, the value of AST between 452 +/- 71 U/L, the TBiL at about 77.1 +/- 14.3 mumol/L. All these showed that only HGV infection could lead to acute hepatitis. The rising enzyme dropped to normal about a month later in acute hepatitis while HGV RNA would remain. The problem whether HGV infection is caused by simple acute and chronic hepatitis infection is under investigation.