2010-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/659873摘要：在台灣，第一型人類免疫不全病毒（HIV-1）的感染人數自從2004 年在藥癮族群中爆發流行後，便急遽地增加。根據我們之前的分子流行病學研究發現，在中國藥癮族群間流行的HIV-1 重組亞型CRF07_BC，很可能是造成此次台灣大流行的元凶。儘管CRF07_BC 和西方流行的B 亞型之間的序列變異已被許多研究所證實，迄今我們對於其表現型及病毒毒性仍所知甚少。因此，本篇計劃首先將進行CRF07_BC 的功能性分析，包含其生長動力學、輔受體的使用、p6 基因中央區域的刪除所造成的影響、及其引發淋巴球細胞凋亡的能力。此外，由於臨床觀察發現，CRF07_BC 感染者的病毒量較其它病毒亞型感染者低，且罕有母子垂直傳染。因此，我們將進一步研究CRF07_BC 表現型及其與臨床表徵之間的關係，如病毒決勝點及疾病的自然進程。同時，為了做為將來藥物使用的參考，我們也將偵測其抗藥性基因型並與B 亞型作比較。最後，由於大多數CRF07_BC 感染者同時感染C 型肝炎病毒（HCV），我們將研究HCV 感染對於HIV 感染自然進程的影響。而GBV-C病毒因與HIV 感染相同宿主細胞，且其共同感染和較慢的HIV 疾病進程有關，故我們亦將探討CRF07_BC 感染者同時感染GBV-C 的可能性及其影響。我們希望藉由分析CRF07_BC 的表現型及其與臨床表徵的相關性，進而對臨床上的病毒毒性及其相關因素有更深入的瞭解。<br> Abstract: Human immunodeficiency virus type 1 (HIV-1) infection in Taiwanwas drastically increased since 2004, due to the outbreak amongintravenous drug users (IDUs) through needle sharing. Based onmolecular epidemiology study, we have identified the recombinant HIV-1,CRF07_BC, which has been circulating among IDUs in China, wasresponsible for the outbreak in Taiwan. Since, little is known about thephenotypes and virulence of CRF07_BC, despite sequence variationsbetween CRF07_BC and subtype B have been documented. In thisproposed research, we would like to aim at determining the functionalcharacteristics of CRF07_BC, which include the growth kinetics,co-receptor usage, effects of unique deletion in the central region of p6,and its capability to induce apoptosis of lymphocytes. Further, sinceclinical observations have pointed out that CRF07_BC infected individualshave relative low viral loads and the mother to child transmission is rare,the correlation of CRF07_BC phenotypes and clinical observations, suchas viral set pint and natural disease progression course, might alsoprovide important information. The pattern of drug resistance genotypeswill also be determined and compared with those of subtype B. Finally,these CRF07_BC infected individuals were likely to be co-infected withHCV at the same time since more than 95% of these individuals aresero-positive for anti-HCV antibody. The influences of HCV co-infection inthe natural course of CRF07_BC infection will be determined. Thecontribution of GBV-C co-infection, which share the same host as HIV-1and has been shown to be correlated with slow disease progression, willalso be examined. By characterizing the CRF07_BC phenotypes, wehope to have a better understanding about its clinical virulence and thepossible viral factor(s) contributing to that.