SM Virology

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The Oncogenesis of John Cunningham Virus

The John Cunningham Virus (JCV) was isolated in culture from the brain of a case of Progressive Multifocal Leukoencephalopathy (PML) complicating Hodgkin’s disease. JCV contains icosahedral capsids that are composed of three structural viral proteins and small, circular, double-stranded DNA genomes. JCV is a member of the polyomaviridae family and infects a large proportion of the population worldwide and may cause PML upon immunodeficiency. When the immune system is defective, JCV may be activated. JCV can be found in tonsillar tissue, and the respiratory and digestive tracts are deemed to be the leading sites for JCV to enter human body. Transgenic mouse model showed that T antigen might induce lung and lens tumors with tissue specificity, which is not linked to alternative splicing of its intron. Taken together, T antigen is considered to play a significant role in JCV oncogenesis. In future, we will establish transgenic mice expressing T antigen in various cells using cell-specific promoter and clarify the pathomolecular mechanisms of T-antigen-related tumors and its tissue specificity of oncogenesis.

Lei Fang1 and Hua-chuan Zheng2*


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Effects of Antiviral Treatment on Chronic Hepatitis B-Related Hepatocellular Carcinoma and Recurrence after Surgical Treatment

Hepatocellular Carcinoma (HCC) is one of the most common and aggressive malignancies, and the high rate of recurrence is a major obstacle to improving prognosis. Chronic Hepatitis B Virus (HBV) is one of the major causes of HCC, and high viral replication rate and related hepatic inflammation are major risk factors of HCC recurrence after surgical resection. Current approved antiviral medications for the treatment of chronic hepatitis B are interferon-α (IFNα) and nucleos (t) ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir, and tenofovir disoproxil fumarate. IFNα treatment significantly reduces HBV-related HCC in sustained responders, but its usage is limited by adverse effects. NAs treatment significantly reduces disease progression into cirrhosis and thus HCC incidence, especially in HBV e antigen-positive patients. However, the long-term continuous treatment of NAs may result in drug resistance due to viral mutations. The effect of IFNα treatment on HCC recurrence remains controversial, while evidence has suggested that postoperative NAs therapy can improve both recurrence-free survival and overall survival in patients with HBV-related HCC. There is a great need to develop more effective and affordable new agents with a better safety record. More high-quality prospective trials are needed to quantitatively estimate treatment efficacy and identify predictive factors of HCC development and progression.

Xiaomei Hou1, Jue Wang2 and Yan Du2*


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Advances in GCRV Research: Virus Molecular Type and Immunogen

Grass carp reovirus, GCRV, belongs to the genus Aquareovirus (AQRV). It is the most virulent species of AQRV, and infection by GCRV causes hemorrhagic disease in grass carp. A new strain, GCRV-GD108, was found in China. Significant differences were found between GCRV-GD108 and GCRV as well as between GCRVGD108 and other known AQRVs. Moreover, similarities were found between GCRV-GD108 and Orthoreovirus (ORV), suggesting a closer evolutionary relationship between GCRV-GD108 and ORV than between GCRVGD108 and the known AQRVs. The discovery of different virus molecular types of GCRV indicates the importance of molecular diagnosis and the development of a specific vaccine. Vaccines have been developed that include inactivated tissue vaccines, inactivated cell vaccines, and attenuated viral vaccines. Great efforts have been made in recent years to investigate immunogen for the preparation of genetically engineered vaccines, which are expected to provide protection for the cultured grass carp.

Xing Ye*and Yuan-yuan Tian


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The Power of GPR for Predicting Liver Fibrosis and Cirrhosis May Be Affected By Different Scoring Systems of Liver Fibrosis in Patients with Chronic Hepatitis B

We read with interest the article by Maud Lemoine et al [1] recently published in Gut. They found that Gamma-Glutamyl Transpeptidase (GGT)-to-Platelet Ratio (GPR) may be acted as a simple, non-invasive and inexpensive alternative to liver biopsy and Fibro scan laboratory model in sub-Saharan Africa. The GPR was significantly better than Aspartate Transaminase-To-Platelet Ratio Index (APRI) [2] and Fib-4 (based on age, ALT, AST and platelet count) [3] in predicting liver extensive fibrosis (≥F2) and cirrhosis (≥F4) in patients with Chronic Hepatitis B (CHB) in the Gambia and Senegal, but not in France. So we hypothesized that the predictive efficiency of these 3 markers may be heterogeneous in different race.

Xueping Yu1,2, Jiming Zhang2* and Zhijun Su1*


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Vital Role of Phylogenetic Analysis as Evidence in Illegal Investigation of Virus Transmission

During recent years phylogenetic analysis has become progressively popular as a tool for the criminal investigation of viral transmission, where it is used to derive the ancestral relationships of viral infections from sampled genome sequences. It has been used to cases involving the transmission of the fast-evolving human immunodeficiency virus (HIV) [1], Hepatitis B Virus (HBV) [2,3], hepatitis E (HEV) [4] and for tracking viral transmission in animal field. For example, for the first time phylogenetic analysis determined that the source of viral disease in aquaculture [5,6,7]. Aspects of the transmission of these viruses are impressed on the genetic variation of genomes [8]. These data revealed information about the patterns of virus emergence, viral epidemiology and evolutionary dynamics [9,8]. Analysis of molecular phylogenetic relationships must be based on a domain with a suitable level of evolution for the issue under investigation. Evaluation of recent transmission events requires the analysis of fast-evolving regions, whereas older events must be studied by sequencing more stable regions [2]. This analysis investigates small difference in virus genome using computational methods to calculate the variation between strains of viruses. This process is a critical complex scientific process which undertaken by virologist. The result of phylogenetic analysis has recently applied in illegal trials as evidence of responsibility for virus transmission [10]. In these events, the expert analysis of virologist has been discovered to be of critical importance. In the other hand, these trials can be applied to acquit individuals and keep out the possibility that defendant was responsible for virus transmission [10,11,8]. It is important to note that molecular analysis cannot prove the transmission virus between two individual, but it can support any information on the direction of that transmission [10,1]. It is necessary for molecular phylogenetic analysis to use the right comparison samples, because inappropriate samples could overstate the relationship between two viruses (of different geographical origin) as being conspicuously unique. In addition, many viruses frequently recombine and cause further opportunity for genetic novelty viral transmission from data commonly based on phylogenetic analysis [8]. Also, models of virus transmission and early diversification are the most important result of phylogenetic study. For example, Zika virus emerged in Africa and now circulates on all inhabited continents [12,13]. In another study demonstrated that isolated Dengue virus type 1 strain from Indonesia has a close phylogenetic relationship with strains of Japan [14]. In the recent decade, phylogenetic studies have matured with focus on the human RNA viruses such as influenza virus, HIV, dengue virus and HCV [8-10,15]. However, there are wide ranges of viruses to which phylogenetic analysis are used [9,16-18]. This review shortly outlines the importance of phylogenic analysis for viral transmission with focus on virus origin and shows phylogenetic approach to identify ecological and biological of virus transmission.

Maryam Dadar*