HCV Case Study

Hepatitis C virus (HCV) is from the virus family Flaviviridae with an RNA envelope serving as it's genetic material. The genetic material (RNA) is HCV's pathogenic structure. The genome is positive sense single stranded RNA, which is very similar to mRNA and can be translated quickly to the host cell (Bauman 2012). Hepatitis C is an enveloped virus, and the RNA also lacks a proofreading ability after replication, which results in mutations coding for many genotypes within the host. This genetic variability makes it difficult for the host immune system to clear all the HCV infections. As one infection clears, another strain is being produced (Bauman 2012). The HCV antibody detected by ELISA(Wilkinson

The increasing number of citizens that are testing positive for Hepatitis C is shocking and the epidemic is just getting worse. One out of every one hundred people in the general population has Hepatitis C, but the ratio is higher in prisons. One out of every six inmates has Hepatitis C (Wegner, Rottnek, Parker and Crippin, 2014). Hepatitis C (HCV) is a blood disease that is caused by a virus and it affects the liver. Unfortunately there is no vaccine to prevent this disease and I have seen first-hand how ugly this virus is. I have worked in the medical field for the past 6 years and I have a very close friend who contracted HCV. Unfortunately, she was one of the many people that needed a liver transplant. HCV has infected four times as

HSV is part of the family herpetoviridae and the genus simplexvirus. There are two strains of this virus: HSV1 known as the oral infection and HSV2 known as the genital infection. The structure of the virus is an enveloped, icosahedral capsid, and single linear double-stranded DNA. The capsid contains dsDNA, α and β proteins. The α proteins regulate the reproductive cycle and block the presentation of antigenic peptides on the host membrane. The β proteins are in charge of the viral nucleic acid metabolism and capsid proteins. The glycoprotein spikes are gB, gC, and gD. There are many modes of transmission of the virus like

Until 2011, the main therapy against the infection was Pegylated-interferon (Peg-IFN) and the ribavirin (RBV) treatment (11). Interferon is a type of protein that stimulates the immune system and helps halt the virus from spreading throughout the body. Pegylated-interferon is a combination of three types of interferon, including polyethylene (PEG), which helps the treatment remain in the body for a longer time period. Ribavirin is a medication that helps stop the HCV virus from replicating. It is commonly used in combination with interferon, which is referred to as the “Peg/riba therapy.” This combination therapy is more effective than the interferon itself. However, these medications do not have a one hundred percent cure rate and it was reported

HSV is a human nuclear DNA virus that can replicate in many different species of animal as well as in many different types of cells. It can gain access to different types of cells due to its 12 envelope surface glycoproteins and uses the heparan moiety of the receptors to attach to cells

A recombinant-based assay for the hepatitis C virus HCV has been developed, using RNA isolate from the hepatitis C virus.

Hepatitis C affects millions worldwide. Hepatitis C causes infection leading to chronic liver disease. Human hepatocyte chimeric mice were made by transplantation of the human hepatocyte to mice. Reverse genetic hepatitis C viruses of two different genotypes were made from infectious clones and human hepatocyte chimeric mice. Chimeric mice were injected with both genotypes of hepatitis C. There after treatment by interferon was administered. A control of human serum from a donor with chronic hepatitis C was used. The results obtained showed that mice injected with both genotypes of hepatitis C virus had a quantifiable level of virus present in the blood. It was observed that genotype 1 did not response to interferon therapy as compared to genotype 2. Results showed a decreased level of genotype 2 of hepatitis C virus after

The Hepatitis B virus (HBV) is a species of the genus Orthohepadnavirus that is transmitted via blood and bodily fluids. It affects the liver by causing a wide range of diseases, “from acute hepatitis (including fulminant hepatic failure), to chronic hepatitis, cirrhosis and potentially hepatocellular carcinoma” (Liang, 2009).

Within cell culture it was shown to be 10 times more potent than Acyclovir (11). Phase I of the clinical trials showed the HSV replication was inhibited within the tested dosing region. It was also concluded the drug stayed in its active form up to 80 hours, far greater than Acyclovir with no reported negative side effects (1). Within the Phase II placebo controlled trial it was reported that viral sheading and lesion rates were decreased in a dose dependent manner. Even though the trial was considered small with only 156 subjects, no adverse effects or viral resistance was reported. Clinical isolates have remained treatable by Pritelivir, but their have be instances for resistance selected for in tissue culture (14). As for updates for resistance, one mutation has been reported in the helicase gene although this has remained in cell culture (15). Although cell culture does have a higher tendency to select for resistance, this dose raise the issue of utility for the novel drug down the line. AIC316 is expected to enter into into Phase III of the clinical trials within the near future. With the clinical trials still proceeding on AIC316 safety is still being evaluated, and strategies are still being devised. All options are being investigated such as combination therapies with current therapies to decrease the chance of resistance

Regina is a 62-year-old female diagnosed with chronic viral Hepatitis C (B18.2) and is genotype 1a. She is treatment naïve. Her most recent lab results indicate HCV RNA 4,005,368 IU/mL, ALT 63, and AST 83. Regina’s CT scan shows a cirrhotic appearance of the liver.

Hepatitis C virus (HCV) Flaviviridae family comprises of positive sense single-stranded RNA ((+)ssRNA) infects 3% of the world population that leads to the liver cirrhosis [1]. There is no permanent cure available till date [2]. Many drug

CDC 's national strategy to prevent HCV infection includes 1) prevention of transmission during high-risk activities (e.g., injection-drug use and unprotected sex with multiple partners) through risk-reduction counseling, testing, and appropriate medical management of infected persons; 2) donor screening and product inactivation procedures to eliminate transmission from blood, blood products, donor organs, and tissue; and 3) improved infection control practices to further reduce risk of transmission during medical procedures † (10).

Markers of HCV infection are found in 80 to 90% of patients with hepatocellular carcinoma in Japan, 44 to 66% in Italy, and 30 to 50% in the United States (El-Serag and Rudolph,2007). It has been projected that cases of HCV-related hepatocellular carcinoma will continue to increase over the next two to three decades (El-Serag

Daclatasvir displayed potent inhibitory activity against all HCV genotypes tested (genotypes 1-6) [18, 19]. In replicon assays, the half~maximal effective concentration (EC5O) values of daclatasvir against HCV genotypes 1a, lb, 2a,3a, 4a and 5a were 50, 9, 71-103, 146, 12 and 33 pmol/L, respectively [28]. Daclatasvir displayed additive or syneregistic inhibitory activity in replicn assays when used in combination with peginterferon-a and ribavirin, NS3/4A inhibitors (danoprevir or asunaprevir) or NSSB inhibitors [EMS-791325 (beclabuvir) or NM-107] [28, 30]

TOUCHTABLE & UI/UX DESIGN : TECHNICAL REPORT ( BY RISHABH ) Declaration TABLE OF CONTENTS DECLARATION I TABLE OF CONTENTS II ABSTRACT V 1 INTRODUCTION 1 1.1 HEPATITIS C VIRUS 1 1.1.1 DISCOVERY 1 1.1.2 EPIDEMIOLOGY 2 1.1.3 PATHOGENESIS 2 1.1.4 TREATMENT 3 1.2 MOLECULAR BIOLOGY 3 1.2.1 STRUCTURE OF GENOME 3 1.2.2 GENETIC VARIATION 6 1.2.3 GENOTYPIC DIFFERENCES 8 1.3 RNA DEPENDENT RNA POLYMERASE ACTIVITY 9 1.3.1 POLYMERASE FUNCTION 9 1.3.2 MODEL SYSTEMS OF HCV REPLICATION 11 1.3.3 GENOTYPE SPECIFIC STUDIES 11 1.3.4 BIOCHEMICAL PROPERTIES 12 1.4 KUNJIN VIRUS RNA DEPENDENT RNA POLYMERASE 13 1.5 CONCLUSION 15 1.6 AIMS AND HYPOTHESIS 16 2 MATERIALS AND METHODS 17 2.1 HCV POSITIVE SERA SAMPLES 17 2.2 RNA EXTRACTION 17 2.3 CDNA SYNTHESIS 17 2.4 HCV PRIMER DESIGN AND USAGE 18 2.5 NESTED POLYMERASE CHAIN REACTION (NPCR) 21 2.5.1 REACTION AND CYCLING CONDITIONS 21 2.5.2 PCR