动物模型,丙型肝炎病毒 z-bo 2020-11-30 350

　　The two human HCV receptors, CD81 and OCLN, were expressed in the liver of ICR mice using transgenic methods. Such mice can support persistent HCV infection and show a similar hepatitis C disease process to humans: acute infection-liver steatosis-liver fibrosis-cirrhosis. This is the world's first animal model of persistent HCV infection that fully reflects the natural history of HCV infection and the progress of chronic viral hepatitis, and will strongly promote the development of vaccines and drugs for hepatitis C prevention and treatment.

　　40 years ago, Harvey Alter of NIH in the United States described non-A, non-B viral hepatitis (NANBH) for the first time; 27 years ago, the Michael Houghton team of Chiron Corporation in the United States cloned hepatitis C virus (HCV) and launched HCV detection technology , HCV diagnosis and treatment have gone for nearly half a century. Nevertheless, due to HCV menstrual blood infections are usually asymptomatic, coupled with low economic and medical level countries and regions with low hepatitis C prevention and control capabilities, there are currently nearly 200 million people worldwide and more than 40 million people in my country carry HCV. Chronic hepatitis C is the main cause of liver cirrhosis and liver cancer. The HCV pandemic has become a huge burden on public health in modern civilized society and a major threat to population health.

　　Although the antiviral treatment of chronic hepatitis C is effective, the toxic and side effects of the drug are large, and the virus rebounds when the drug is stopped. The release of new drugs is far behind the emergence of drug-resistant mutants. The complete elimination of HCV is only a dream. What's more worrying is that, like HIV, it is very difficult to develop vaccines against such highly mutated RNA viruses that can escape immune killing. In the past 10 years, scientists have been exploring animal models of HCV infection. However, HCV only infects humans and chimpanzees. The various experimental mouse models that people are trying to establish either HCV virus cannot replicate, or the immune system of mice is defective, or there is no chronic hepatitis C pathology. Therefore, an animal model of persistent HCV infection has been developed to ascertain how HCV continues to infect and cause liver damage, and is used in the development of vaccines and drugs.

　　Chen Xinwen and Tang Hong pointed out that the success of this model not only provides the most advanced materials to reveal the pathogenic mechanism of hepatitis C, but will undoubtedly promote the development of vaccines and drugs for the prevention and treatment of hepatitis C. It is the Chinese scientists' contribution to the threat to human society. A landmark contribution to the research of major infectious diseases.

　　The doctoral student Chen Jizheng who participated in the research pointed out, “Such mouse liver cells express two receptor molecules for HCV entering liver cells, CD81 and OCLN, through transgenic technology. HCV virus isolated from patient serum can enter mouse liver cells. It is highly replicated. Viremia has appeared in the liver and peripheral blood of mice, and it has lasted for nearly 2 years." Even more tempting is that another assistant researcher Zhao Yang who participated in the study pointed out that “80% of the mice can be continuously infected by HCV, and typical HCV acute infection and chronic pathological progress have occurred, including one after infection. Fatty liver that appears in 1 month, liver fibrosis that begins in 3 months, and cirrhosis that appears in 6 months. This is unimaginable in other animal models, including chimpanzees." Another team member, Dr. Chao Zhang, added, "We have been able to observe in mice how HCV escapes the immune system, and how antiviral drugs reduce the virus titer."