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The Coronaviridae family includes viruses that are considered the causative agents of respiratory infections, and among human RNA viruses have the largest genome. Coronaviruses undergo elusive genetic changes through mutation during replication. A gene mutation is a permanent alteration in the nucleic acid sequence; if it occurs in large numbers, it causes changes in the biological features of a species. Fundamentally, viruses adapt to the human body during replication. Several studies have shown that most mutations do not have much effect on pathogenicity. Sequence diversity in new coronaviruses is very low. However, antigen drift has been observed among some coronaviruses. Most coronavirus mutations occur intermittently in Iran and other
BackgroundActivation of the immune system to fight cancer is a major goal in immunology and oncology. Although cancer treatment using oncolytic viruses shows promising results, virus mediated oncolysis induces a weak anti-tumor immune response. Upon application of viruses, immune responses against the virus play a significant role in limiting tumor virotherapy. Although suppression of host immunity increases the efficacy of virotherapy against the tumor, but inhibits anti-tumor immune responses. Induction of viral specific tolerance before viral replication may cause the virus to efficiently replicate in tumor cells without affecting the immune responses against tumor antigens. Investigation of the combined strategy of virotherapy and immun
Interferon lambda was discovered in recent years to be an antiviral agent, and research on different aspects of this antiviral factor in viral infection and investigations of its effectiveness are also progressing. The immunological effects of interferon lambda on different cell populations is not precisely known, which may be due to its use of a heterodimeric receptor consisting of IL-10R2 and IFN-λR1, which are not broadly expressed in all types of cells. In the present study, signaling by interferon lambda and its effect on the expression of hepatitis C virus (HCV) proteins were measured, and the expression pattern of some antiviral proteins and IL-10 levels were investigated in peripheral blood mononuclear cells (PBMCs). PBMCs were iso
Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and aggravates disease consequences in alcohol‐abusing patients. Although the exact reasons by which alcohol consumption affects several cellular pathways in liver cells are not clear, they might be partially attributed to the ability of alcohol to further suppress the innate immunity, modulation of autophagy and also its relationship with reactive oxygen species (ROS) generation. To evaluate these issues, Huh7 cells harboring HCV replicon and Cytochrome p450 (CYP2E1) plasmid were exposed to ethanol and mRNA expression of Beclin-1, interferon-stimulated gene15 (ISG15) genes?and HCV NS5B for two different times were relatively quantitated. ROS was determ
Background: Hepatitis C virus (HCV) is a significant cause of chronic inflammatory liver diseases. Hepatitis C virus infection is a common disorder worldwide, which has become a significant public health concern. The survival of viruses in host cells is associated with their ability to engage in cellular mechanisms benefitted from.Objectives: This study aimed at evaluating the expression rate of Beclin 1, as a critical protein of autophagy, and its correlation with interferon-alpha (IFN-α) expression in both IFN-ribavirin responder and non-responder groups.Methods: In this study, a total of 40 samples of the peripheral blood mononuclear cells (PBMCs) were evaluated. Twenty samples were collected from the patients with chronic HCV as non-re
Earlier observation suggests that Hepatitis C virus (HCV) is a single‐stranded RNA virus which encodes at least 10 viral proteins. F protein is a novel protein which has been discovered recently. These studies suggest 3 mechanisms for the production of this protein concerning ribosomal frameshift at codon 10, initial translation at codon 26, and 85 or 87. In this study, the association between protein F and chronicity of hepatocellular carcinoma (HCC) has been reviewed. Evidence suggests that humoral immune system can recognize this protein and produce antibodies against it. By detecting antibodies in infected people, investigators found that F protein might have a role in HCV infection causing chronic cirrhosis and hepatocellular carcin
A growing area of research is focused on cancer therapy, and new therapeutic approaches are welcomed. Mesenchymal stem cell (MSC)-based gene therapy is a promising strategy in oncology. Intrinsic tropism and migration to tumor microenvironment with off lights are attractive features of this type of cell carrier. In this way, suicide genes have also found a good platform for better performance and have shown a stronger anti-tumor mechanism by riding on mesenchymal cells. In this study, we investigated the anti-tumor activity of intratumoral injected MSCs transduced with a lentivector expressing the HSV/TK in a mouse cervical cancer model. Following the injection of MSCs transduced with lentivector carrying TK, MSCs alone or PBS into the mice
Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from treatment-naive HCV-infected patients. The cells were treated with different doses of Interferon alpha 2a (IFN-α 2a) and the mRNA expression of target genes (ISG15, MXA, PKR and OAS) at different time points was evaluated by Real Time PCR. The levels of ISG15 and OAS were measured in culture supernatant using ELISA and the level of HCV NS5A in chronic HCV patients was measured by flow cytometry.Results: Our results showed that IFN-α 2a effect on the expression of antiviral proteins was dependent on dose and time of administrated IFN-α.Conclusions: This finding indicates that IFN-α should be used at optimal dose to achieve the best efficiency and establi
Background and Aims: Interferon alpha is an effective cytokine in viral infections, where it has various roles in immune function. The use of this antiviral agent in the treatment of viral infections and even cancers is common, although, the beneficial effects of this antiviral agent in high doses can be associated with side effects that limit its use. In this project, we tried to investigate the effects of different doses and timing of interferon alpha treatment on the expression of downstream interferon signaling genes and evaluation of the antiviral effects in patients with chronic hepatitis C.Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from treatment-naive HCV-infected patients. The cells were treated
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are among the most dangerous pathogens globally. Infection with HCV has been reported in a high percentage of HIV patients. Viruses are obligate intracellular pathogens and their survival is associated with their capability to subvert antiviral defenses of cells and to improve cellular processes required for their replication. The aim of this study was to compare the expression rate of the key gene for autophagy process, Beclin-1, as a cellular response to viral infections, and its effect on IFN-α expression in both HCV and HCV/HIV patient groups. In this study, a total number of 40 samples of peripheral blood mononuclear cells (PBMCs) including 20 HCV and 20 HCV/HIV patients b
Hepatitis C virus (HCV) is a major health problem all over the world. Among HCV proteins, nonstructural protein 3 (NS3) is one of the most promising target for anti‐HCV therapy and a candidate for vaccine design. DNA vaccine is an efficient approach to stimulate antigen‐specific immunity but the main problem with that is less immunogenic efficiency in comparison with traditional vaccines. Several approaches have been applied to enhance the immunogenicity of DNA. Recently, bacteria‐derived substances are considered as one of the most attractive adjuvants for vaccines, which among them, Listeriolysin O (LLO) of Listeria monocytogenes is a toxin with an extremely immunogenic feature. We investigated detoxified form of LLO gene as geneti
There is a relationship between the life cycle of the hepatitis C virus (HCV) and the synthesis and hemostasis of lipids as well as lipid metabolism and interferon (IFN) regulatory system. This study aimed to examine the effect of fluvastatin and IFN-ƛ in the expression of mediators involved in lipid metabolism and HCV proliferation in patients with rs12979860 CC polymorphism.
Nucleic acid immunization has recently exhibited a great promise for immunotherapy of various diseases. However, it is now clear that powerful strategies are imminently needed to improve their efficiency. In this regard, whole bacteriophage particles have been described as efficient DNA vaccine delivery vehicles, capable of circumventing the limitations of naked DNA immunization. Moreover, phage particles could be engineered to display specific peptides on their surfaces. Given these inherent characteristics of phages, we have designed a novel hybrid phage-DNA immunization vector using both M13 and pAAV plasmid elements. Following the construction and in vitro confirmation of the designed vectors, they were used for comparati
Aims of the StudyThe major problem of? DNA vaccine is less immunogenic than older style live or killed whole organism vaccines therefore adjuvants? for use in this kind vaccines is very necessary. Genetic adjuvants with bacterial sources are an appropriate approach to modulate immune responses to DNA vaccines. Listeria Monocytogenes proteins such as Listeriolysin O (LLO) with CD4 and CD8 epitopes can be as an adjuvant to initiate both innate and adaptive immune responses if the protein cytotoxicity can be elimitated. Herein we constructed a truncated LLO plasmid as genetic adjuvant.Materials & MethodsAbout 1340bp of? the 5' end of whole LLO gene was amplified by PCR on DNA purified from Listeria Monocytogenes. Sequential subcloning of trunc