Hepatitis C: A mouse at the end of the tunnel
Worldwide,over 130 million people are chronically infected with Hepatitis C virus (HCV).Acute infection goes along with mild and generalized symptoms,and therefore mostly remains undiagnosed;in more than half of the patients,however,the infection persists and,over the years,can cause liver damage such as fibrosis,cirrhosis or hepatocellular carcinoma.
HCV is a positive strand RNA virus of the family Flaviviridae.Studies of this virus have made huge leaps forward since the implementation of efficient cell culture systems [1,2];nonetheless,our knowledge of HCV-associated pathogenesis is scarce owing to the lack of a practicable animal model.So far,chimpanzees are the only animals fully susceptible to HCV infection;however,legal,ethical,economical let alone practical reasons dictate the establishment of small animal models as an altemative.Most efforts have been put into various mouse models [3],but in general,mice are resistant to HCV infection.Only individual steps of the lifecycle could be reproduced in mouse cells:expression of human variants of the entry receptors CD81 and occludin mediates virus uptake into mouse cells [4,5];selectable replicons demonstrated that HCV RNA can be replicated in mouse cells,albeit inefficiently;and assembly as well as secretion of HCV particles can be achieved in mouse hepatocytes [3].In contrast,for studying the full replication cycle in living animals,systems had to be developed,in which mouse hepatic tissue was inducibly or constitutively deteriorated to allow repopulation by human hepatocytes [3].This interspecies chimerism naturally required the animals to be immuno-deficient to avoid graft rejection.Nonetheless,particularly the uPA-SCID model has become very popular,especially for pre-clinical drug testing and validation and for studying passive immunization strategies against HCV infection.Still,for research on vaccine development and pathogenesis,these models are of limited to no use,as such studies require robust immune responses.
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2014-01-23（万方平台首次上网日期，不代表论文的发表时间）
共2页
1343-1344
