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Carrying the RT gene of HIV-1 epidemic strain new of SHIV build and biological characteristics of

Author: YaoNan
Tutor: WeiQiang；QinChuan；LiWanBo
School: Beijing Union Medical College
Course: Zoology
Keywords: RT-SHIV Chinese prevalent HIV-1 strain animal model drug selection drug resistance
CLC: R512.91
Type: Master's thesis
Year: 2011
Downloads: 15
Quote: 0
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Abstract

Anti-virus drug therapy has been playing the dominant role for the treatment of AIDS patients. The most popular drugs are the inhibitors for reverse transcriptase, and the main target of the inhibitor is reverse transcriptase gene. Many of new exploited inhibitors have showed high effectiveness against HIV in the cell level, and need the specific SHIV/rhesus model to evaluate the real treatment effect in vivo and the possible drug resistance. The purposed SHIV should contain HIV drug target. RT-SHIV is a new virus which has an SIV backbone and rt gene from HIV. containing anti HIV drug specific target-rt gene is the main characteristics of this chimeric virus. RT-SHIV/rhesus model can be used as a human HIV targeted evaluation system for selection of inhibitor of reverse transcriptase in vivo. At the same time we can monitor variations of rt gene at the present of various inhibitors, and apply the research platform of RT-SHIV/rhesus model for the resistance analysis. This thesis has finished with two parts:the first part is that the Chinese origin rhesus model has been established with the infection of RT-SHIV/TC. The second part is about the construction of a SHIV that contains an rt gene from HIV-1 prevalent in China and its infectious research both in vitro and in vivo.In the first part, the characteristic of this virus in vitro such as virus proliferation, virus titration and drug selection were studid. RT-SHIV/TC/Chinese origin rhesus model has been created successfully through RT-SHIV/TC infection and virus passaging in vivo. By using this model, the inhibitor drugs against reverse transcriptase were medicated for treatments of emergency prevention and chronic duration, respectively. We also found that the SHIV proliferated by PBMC showed greater virulence than proliferated by CEMx174. and the virulence of SHIV could be enhanced by passaging in monkeys. We have tested the virus sensitivety of inhibitor of reverse transcriptase. In conclusion, in this part RT-SHIV/TC/Chinese origin rhesus models for drug selection have been constructed via both of vein and mucosal routes.In the second part, SIVmac239 was used as a backbone to construct the RT-SHIV from which the corresponding region was replaced by HIV-1 rt gene prevalent in china. The rt gene was amplified from HIV-1 plasmid or HIV. We have constructed 5 types of RT-SHIVs, and transfected 293T by chimeric plasmid. harvested supernatant, tested the activity of constructed virus by TZM-bl. The RT-SHIV/AE has demonstrated the high infection activity, and also in CEMx174 and PBMCs from monkeys. This virus has CCR5 tropism with determination of GHOST cell line. At the last. RT-SHIV/AE was used to infect Chinese origin rhesus monkeys, and the result showed that monkeys could be infected by RT-SHIV/AE.In conclusion, the RT-SHIV/AIDS non-human primate models were established by using different types of HIV, this model system is useful for drug selection and resistance analysis, especially for the comparative studies both from China and the other region.

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CLC: > Medicine, health > Internal Medicine > Infectious disease > Viral infections > Acquired Immune Deficiency Syndrome ( AIDS AIDS)
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