By analogy to other members of the Flaviviridae family, the hepatitis C virus (HCV) core protein is presumed to oligomerize to form the viral nucleocapsid, which encloses the single-stranded RNA genome. Core protein is directed to lipid droplets (LDs) by domain 2 (D2) of the protein, and this process is critical for virus production. Domain 1 (D1) of core is also important for infectious particle morphogenesis, although its precise contribution to this process is poorly understood. In this study, we mutated amino acids 64 to 75 within D1 of core and examined the ability of these mutants to produce infectious virus. We found that residues 64 to 66 are critical for generation of infectious progeny, whereas 67 to 75 were dispensable for this process. Further investigation of the defective 64 to 66 mutant (termed JFH1 T -64-66) revealed it to be incapable of producing infectious intracellular virions, suggesting a fault during HCV assembly. Furthermore, isopycnic gradient analyses revealed that JFH1 T -64-66 assembled dense intracellular species of core, presumably representing nucleocapsids. Thus, amino acids 64 to 66 are seemingly not involved in core oligomerization/nucleocapsid assembly. Passaging of JFH1 T -64-66 led to the emergence of a single compensatory mutation (K1302R) within the helicase domain of NS3 that completely rescued its ability to produce infectious virus. Importantly, the same NS3 mutation abrogated virus production in the context of wild-type core protein. Together, our results suggest that residues 64 to 66 of core D1 form a highly specific interaction with the NS3 helicase that is essential for the generation of infectious HCV particles at a stage downstream of nucleocapsid assembly.Hepatitis C virus (HCV) typically establishes chronic infections of the liver that frequently lead to severe pathologies, including cirrhosis and hepatocellular carcinoma. The current combination therapy of pegylated alpha interferon (IFN-␣) and ribavirin is only partially effective and is associated with numerous side effects. Treatment for HCV is currently transitioning to the use of direct-acting antiviral (DAA) therapy, which has been specifically designed to target viral proteins essential for HCV replication (30). While early results indicate that DAA compounds show promise, a wider range of treatments targeting multiple aspects of the viral life cycle would offer improved therapeutic options to infected individuals. In this regard, a better understanding of HCV assembly could provide an alternate exploitable target.

Hepatitis C virus (HCV) is a major global health burden with 2-3% of the world's population being chronically infected. Persistent infection can lead to cirrhosis and hepatocellular carcinoma. Recently available treatment options show enhanced efficacy of virus clearance, but are associated with resistance and significant side effects. This warrants further research into the basic understanding of viral proteins and their pathophysiology. The p7 protein of HCV is an integral membrane protein that forms an ion-channel. The role of p7 in the HCV life cycle is presently uncertain, but most of the research performed to date highlights its role in the virus assembly process. The aim of this review is to provide an overview of the literature investigating p7, its structural and functional details, and to summarize the developments to date regarding potential anti-p7 compounds. A better understanding of this protein may lead to development of a new and effective therapy.

The hepatitis C virus (HCV) genome encodes a 63 amino acid (aa) protein, p7, which is located between the structural and non-structural proteins. p7 localizes to endoplasmic reticulum membranes and is composed of two transmembrane domains (TM1 and TM2) and a cytoplasmic loop. While its exact role is unknown, p7 is crucial for assembly and/or release of infectious virus production in cell culture, as well as infectivity in chimpanzees. The contribution of p7 to the HCV life cycle may result from at least two distinct roles. Firstly, several studies have shown that p7 acts as an ion channel, the functionality of which is critical for infection. Secondly, p7 interacts with NS2 in a manner that may regulate the targeting of other structural proteins during the assembly process. In this study, we observed that mutations in TM1 and the cytoplasmic loop of p7 decreased infectious virus production in a single-cycle virus production assay. Analysis of intra- and extracellular virus titers indicated that p7 functions at a stage prior to generation of infectious particles. These effects were not due to altered RNA replication since no effects on levels of NS3 or NS5A protein were observed, and were not a consequence of altered recruitment of core protein to lipid droplets. Similarly, these mutations seemingly did not prevent nucleocapsid oligomerization. Importantly, we found that an alanine triplet substitution including the two basic residues of the cytoplasmic loop, which is integral to p7 ion channel function, significantly reduced E2 glycoprotein levels. A time course experiment tracking E2 levels indicated that E2 was degraded over time, as opposed to being synthesized in reduced quantities. The results of this study provide strong evidence that one of the functions of p7 is to protect HCV glycoproteins from premature degradation during virion morphogenesis.

Context: Much attention has been given recently to the antioxidant capacity of natural products, with particular interest on those that are frequently consumed by people. Aims: To evaluate the commonly used and frequently consumed edible herbs in Jordan to compare their in vitro and in vivo antioxidant properties. Methods: The in vitro antioxidant properties were tested by pre-incubating washed human erythrocytes with a given herb extract and then exposing these erythrocytes to H2O2 to induce oxidative stress, and then measuring erythrocyte malondialdehyde (MDA) as a marker for lipid peroxidation, protein carbonyl (PC) as a marker for protein oxidation, reduced glutathione (GSH) as a marker for cellular antioxidant status and the percentage of hemolysis as an indicator for the anti-hemolytic activity of the herb. The in vivo antioxidant properties were tested by giving orally aqueous extracts of the herbs tested in vitro to healthy individuals on daily bases for five days, with two blood samples being collected from each individual to measure the above-mentioned markers. Results: Pre-incubation of human erythrocytes in vitro with methanolic extracts of Zingiber officinale, Rosmarinus officinalis, Salvia triloba, Verbena triphylla, Nigella sativa and Origanum syriacum significantly improved erythrocyte MDA, PC and oxidant hemolysis. Oral consumption by healthy individuals of aqueous extracts of the same herbs for 5 days significantly improved erythrocyte MDA, GSH, and superoxide dismutase (SOD) at the sixth day of administration. Conclusions: These results indicate that aqueous extracts of medicinal herbs can be absorbed well and appear in body tissues inflecting in vivo antioxidant properties similar to their in vitro properties.

Background: The national mandatory premarital screening test is based on MCV > 80fL value for the detection of β-thalassemia to provide acceptance for marriage. The objective of this study is to assess the efficacy of MCV as a screening test for β-thalassemia trait in the present population. Methods: This study was conducted on 418 blood samples collected from adult individuals. The diagnosis of β‐thalassemia carrier was given to those having HbA2 values equal to or above 3.5%. The diagnostic reliability of different RBC indices and formulas in discriminating cases of β-thalassemia trait were evaluated. Finally, a new index called “Momani” was determined based on MCV, RDW and RBC count. Results:  β-thalassemia trait was identified in 10 % of the cases. The measured MCV value was significantly lower in β-thalassemia carrier group compared to non-carrier group (p = <0.001). MCV value and RBC count showed a higher diagnostic reliability than other RBC indices. We found that MCV ≤ 74.45fl is more suitable cut off value of MCV with 86.2% specificity, 71.4% sensitivity, 36.6% positive predictive value, and 96.4% negative predictive value. Finally, our index “Momani” was found to be useful in predicting carrier and paralleled the performance of Sirdah, Mentzer, and Ehsani indices. Conclusion: MCV<80 is a useful but not a perfect cut-off point for the screening of β-thalassemia carriers from non-carriers. The diagnostic accuracy of MCV can be improved by selecting a new cutoff value. Moreover, “Momani” index shows good discrimination ability in diagnosing β -thalassemia carrier in our population.