Mechanisms of immune escape in viral hepatitis.
نویسنده
چکیده
WHY IMMUNE ESCAPE IS IMPORTANT Knowledge of the molecular virology of the hepatitis viruses and the responses they elicit has emphasised the importance of host immunity in resolving infection and mediating liver damage. Many viruses cause cytolytic infections in which viral replication occurs at the expense of host cell viability. However this is a shortsighted strategy for the virus as it provides a clear “danger signal” that alerts the host’s innate and adaptive immune defences to eliminate the virus and terminate the infection. Such a life cycle requires a high rate of transmission from host to host, causes acute tissue damage and is unlikely to result in persistent infection. In order to cause chronic infection viruses must use strategies that enable them to evade or modify host immune responses suYciently to prevent clearance. Of the hepatitis viruses only hepatitis B (HBV) and hepatitis C (HCV) viruses cause chronic infections and in order to do so they must evade host immune responses. Neither hepatitis A virus nor hepatitis E virus cause chronic infection and must be assumed to lack the ability to escape immune responses. Understanding the mechanisms used by HBV and HCV to evade host immunity is central to understanding their pathogenicity and necessary for the development of eVective therapeutic strategies. Although knowledge of the mechanisms of immune escape by hepatitis viruses is increasing, considerable insight has come from the study of other viruses, some of which can cause hepatitis such as Epstein-Barr virus (EBV), HIV, and model systems such as murine lymphocytic choriomeningitis virus (LCMV), as well as transgenic mouse models of HBV infection. In both acute HBV and HCV infection a vigorous antiviral T lymphocyte response is associated with viral clearance. In chronic hepatitis B and hepatitis C virus specific T lymphocyte responses are weak or absent. The mechanisms leading to ineVectual T cell responses in chronic viral hepatitis are discussed below.
منابع مشابه
The Effect of SB431542, TGF-β Receptor Inhibitor, on HCV Replication in PBMCs of Patients with Chronic Hepatitis
Background and Aims: TGF-β is an effective cytokine in the viral replication cycle, which is also highly relevant to the pathogenesis of some viral infections. TGF-β induction by viral proteins is one of the ways to escape the virus from the immune system by inhibiting interferon signaling and other immune system factors. In recent years, the role of TGF-β and its inhibitor...
متن کاملInnate and adaptive immune responses in HCV infections.
Hepatitis C virus has been identified a quarter of a decade ago as a leading cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously during acute infection. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN) induced genes, and a delayed ...
متن کاملHepatitis C virus immune escape via exploitation of a hole in the T cell repertoire.
Hepatitis C virus (HCV) infection frequently persists despite eliciting substantial virus-specific immune responses. Thus, HCV infection provides a setting in which to investigate mechanisms of immune escape that allow for viral persistence. Viral amino acid substitutions resulting in decreased MHC binding or impaired Ag processing of T cell epitopes reduce Ag density on the cell surface, permi...
متن کاملThe genetics of hepatitis C virus underlie its ability to escape humoral immunity.
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, and efforts to develop therapeutic vaccine strategies have been limited by immune escape due to HCV variants that are resistant to current vaccines or HCV variants that rapidly acquire new resistance-conferring mutations. Recently, the crystal structure of the viral envelope protein E2 region was resolved as well as how E2 doc...
متن کاملImmunostimulants: Types and Functions
Immunomodulators are natural or synthetic materials that regulate the immune system and induce innate and adaptive defense mechanisms. These substances are classified into two types, immunostimulants and immunosuppressants. Immunostimulants can enhance body's resistance against various infections through increasing the basal levels of immune response. These agents could increase the oxidative a...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Gut
دوره 44 5 شماره
صفحات -
تاریخ انتشار 1999