| Since the identification of HIV(Human immunodeficiency virus) as the pathogen of AIDS in the last two decades of 20th century,AIDS has been a worldwide health problem.After 30 years' hard work of the scientists all over the world,we still have not found an effective way to eliminate the virus or to cure AIDS yet.One reason remains the large chances of mutation of the RNA virus.Secondly,the superinfected virus plays an important role in the replication and transmission of HIV as well as the AIDS progression.In another hand,since the immune compromise induced by HIV,superinfected virus such as herpes virus may cause severe diseases. So it's important to study the molecular mechanism and the anti-virus therapy based on it.Herpesviruses are the most common and dangerous viruses that co-infect with HIV.They are hard to be rid of,can be frequently reactivated and cause severe clinical symptoms.Since 1990s,our lab has been trying to explore the interactions between Lentivirus and Herpesviruses,study the mechanisms by which the proteins encoded by herpesviruses affect the replication of Lentivirus.We found that in BHV(Bovine herpesvirus) bICP0,the counterpart of ICP0 in HSV-1,could catalyze K63-linked ubiquitination.Another protein,TRAF6 which lies upstream of TAK1,can also be activated by K63-1inked ubiquitination.Based on these rules,we assessed whether ICP0 activated TAK1 through its upstream molecule TRAF6.First,we found ICP0 synergies TRAF6's activation of NF-κB.Then we studied the molecular mechanisms of this activation:(1) By co-IP,we found that this two proteins can interact with each other.(2) We also observed that ICP0 promoted the K63-linked but not K48-1inked ubiquitination of TRAF6 in an auto-ubiquitination activity independent way.(3) To investigate which domain of ICP0 is required for ubiquitinating TRAF6 and synergying activation of NF-κB we studied a serious of deletion and mutant of ICP0.We found that the RING domain is important in both events.Third,HSV-1 itself can also promote the ubiquitination of TRAF6.This study partly uncovered the role Of ICPO in Virus repIication and diseases induced by HSV-1. and shed a light on studying the mechanisms of superinfection in the infection and diseases inducing of Lentivius. |
