Production and pathogenicity of hepatitis C virus core gene products

Hepatitis C virus(HCV)is a major cause of chronic liver diseases,including steatosis,cirrhosis and hepatocellular carcinoma,and its infection is also associated with insulin resistance and type 2 diabetes mellitus.HCV,belonging to the Flaviviridae family,is a small enveloped virus whose positive-stranded RNA genome encoding a polyprotein.The HCV core protein is cleaved first at residue 191 by the host signal peptidase and further cleaved by the host signal peptide peptidase at about residue 177 to generate the mature core protein(a.a.1-177)and the cleaved peptide(a.a.178-191).Core protein could induce insulin resistance,steatosis and even hepatocellular carcinoma through various mechanisms.The peptide(a.a.178-191)may play a role in the immune response.The polymorphism of this peptide is associated with the cellular lipid drop accumulation,contributing to steatosis development.In addition to the conventional open reading frame(ORF),in the+1 frame,an ORF overlaps with the core proteincoding sequence and encodes the alternative reading frame proteins(ARFP or core+1).ARFP/core+1/F protein could enhance hepatocyte growth and may regulate iron metabolism.In this review,we briefly summarized the current knowledge regarding the production of different core gene products and their roles in viral pathogenesis.

Analysis of molecular variation in porcine reproductive and respiratory syndrome virus in China between 2007 and 2012

In the present study, 89 porcine reproductive and respiratory syndrome virus(PRRSV) isolates in China during 2007 to 2012 were randomly selected from the GenBank genetic sequence database. Evolutionary characteristics of these isolates were analyzed based on the sequences of non-struc-tural protein 2(Nsp2) and glycoprotein 5(GP5). The genetic variations of the isolates were also compared with six representative strains. The results showed that a high degree of genetic diversity exists among the PRRSV population in China. Highly pathogenic PRRSV isolates, with a discon-tinuous deletion of a 30 amino acid residue in the Nsp2 region, remained the most dominant virus throughout 2007–2012 in China. Owing to the extensive use of representative vaccine strains, natu-ral recombination events occurred between strains. Three isolates – HH08, DY, and YN-2011 – were more closely related to vaccine strains than the other isolates. Both YN-2011 and DY were the evolu-tionary products of recombination events between strains SP and CH-1R. The results of the present study provide useful information for the epidemiology of PRRSV as well as for vaccine development.

Value of T cell receptor gamma alternate reading frame protein and keratin 5 in endometrial carcinoma

Background Tumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma. Methods Ninety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People＇s Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics （FIGO） stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays （SAM） was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by X2 test. Results Analysis between FIGO 1988 stage I and stage III identified a 362-gene ＂progress signature＂; 171 downregulated and 191 up-regulated genes. Among the alterative genes, TARP （T cell receptor gamma alternate reading frame protein） and KRT5 （keratin 5） decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased （P〈0.05）. The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased （P〈0.05）. In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ （both P〈0.05） both. The expression of P53 had a negative relationship with the expression of KRT5 （P〈0.05）, but not with the expression of TARP （P〉0.05）. There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN （all P〉0.05）. There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 （P〉0.05）. Conclusion The expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.