人類免疫缺陷病毒 (HIV) 是人獲得性免疫缺陷綜合征 (愛滋病，AIDS) 的致病原，2010年全球有180萬人死於愛滋病，HIV/AIDS已成為全球健康的嚴重挑戰。人類免疫缺陷病毒與乙型肝炎病毒 (HBV) ，丙型肝炎病毒 (HCV) 的合併感染非常普遍，已演變成具有嚴重臨床後果的新健康問題。儘管對於人類免疫缺陷病毒的研究已有很大的進展，但由於受研究模型的限制，人體免疫系統對人類免疫缺陷病毒感染的應答，特別是對乙型肝炎病毒，丙型肝炎病毒與人類免疫缺陷病毒合併感染的免疫應答，仍值得進一步的闡明。 / 在本研究中，我們首先對深圳人類免疫缺陷病毒，乙型肝炎病毒，丙型肝炎病毒合併感染的流行情況進行研究。共選取914份人類免疫缺陷病毒感染者的血漿，經過對乙型肝炎病毒表面抗原 (HBsAg) 和抗丙型肝炎病毒抗體 (anti-HCV) 的檢測，發現10.9% (100/914) 的被檢測者是人類免疫缺陷病毒/乙型肝炎病毒合併感染，14.6% (133/914) 為人類免疫缺陷病毒/丙型肝炎病毒合併感染，3.7% (34/914) 為人類免疫缺陷病毒/乙型肝炎病毒/丙型肝炎病毒三重感染。多元邏輯回歸分析證明人類免疫缺陷病毒傳染的危險行為與合併感染顯著相關聯。大多數的人類免疫缺陷病毒/乙型肝炎病毒合併感染者都是通過性接觸感染人類免疫缺陷病毒，包括異性傳播與同性傳播 (95/100, 95%); 大多數的人類免疫缺陷病毒/丙型肝炎病毒合併感染者是靜脈注射吸毒者 (89/133, 66.9%); 人類免疫缺陷病毒/乙型肝炎病毒/丙型肝炎病毒三重感染者中，大多數是靜脈注射吸毒者 (28/34, 82.4%)。靜脈注射吸毒人群中，大部分是男性 (108/122, 88.5%)，約半數人的年齡介乎27至32歲 (56/122, 45.9%) 。有接近一半的經過血液和血液製品傳播人類免疫缺陷病毒的人是人類免疫缺陷病毒/丙型肝炎病毒合併感染者 (10/23, 43.5%) 。性別與人類免疫缺陷病毒感染的危險行為有顯著關係，大部份的靜脈注射吸毒者是男性。 / 進一步，我們利用酶聯免疫吸附測定法 (ELISA) 檢測深圳愛滋病陽性樣本血漿中白細胞介素27 (IL-27) 的濃度。結果顯示，對比健康參照者，人類免疫缺陷病毒單獨感染者，人類免疫缺陷病毒/乙型肝炎病毒合併感染者，人類免疫缺陷病毒/丙型肝炎病毒合併感染者的血漿IL-27濃度顯著升高。隨後我們進一步發現，人類免疫缺陷病毒單獨感染組，人類免疫缺陷病毒/乙型肝炎病毒，人類免疫缺陷病毒/乙型肝炎病毒/丙型肝炎病毒合併感染組之間的血漿IL-27濃度沒有顯著差異，而人類免疫缺陷病毒/丙型肝炎病毒合併感染組與人類免疫缺陷病毒/乙型肝炎病毒/丙型肝炎病毒三重感染組的血漿IL-27濃度差異顯著。我們還發現人類免疫缺陷病毒單獨感染組中，血漿IL-27濃度與CD4⁺ T 淋巴細胞數量顯著正相關 (r = 0.177, P = 0.034)。 / 我們進一步分析了人類免疫缺陷病毒和丙型肝炎病毒的病毒載量對血漿IL-27濃度的影響，發現HIV單獨感染組中人類免疫缺陷病毒載量與血漿IL-27濃度沒有顯著相關 (r = - 0.063, P = 0.679)，而人類免疫缺陷病毒/丙型肝炎病毒合併感染組中，人類免疫缺陷病毒載量與血漿IL-27濃度顯著正相關 (r = 0.362, P = 0.049)。人類免疫缺陷病毒/丙型肝炎病毒合併感染組中，人類免疫缺陷病毒載量與丙型肝炎病毒載量缺少顯著線性關聯 (r = - 0.072, P = 0.704)，而人類免疫缺陷病毒/丙型肝炎病毒合併感染組可根據人類免疫缺陷病毒與丙型肝炎病毒的病毒載量再細分成血漿IL-27濃度差異顯著的三組 (P = 0.014) ， 丙型肝炎病毒載量與血漿IL-27濃度缺少顯著關聯 (r = - 0.119, P = 0.530) 。 / 我們利用TaqMan®等位基因分型技術測定深圳男同性戀人群中IL-27 p28基因的單核苷酸多態性 (SNP)。結果顯示，人類免疫缺陷病毒感染組IL-27 p28 -964A/G 和4603G/A的基因型與健康男同性戀參照組的基因型沒有顯著差異， IL-27 p28 -964A/G 和4603G/A的等位基因比率也沒有顯著差異。結果也顯示，IL-27 p28 2905T/G的TG基因型可減少2.77倍的人類免疫缺陷病毒感染風險，等位基因G可減少2.72倍的人類免疫缺陷病毒感染風險。連鎖不平衡在IL-27 p28 -964A/G 和2905T/G 中存在 ( / 綜上所述， 在本研究中，我們首次調查了深圳人類免疫缺陷病毒，乙型肝炎病毒，丙型肝炎病毒合併感染的流行情況，並分析了合併感染的風險因素。 發現人類免疫缺陷病毒單獨感染者，人類免疫缺陷病毒/乙型肝炎病毒合併感染者， 及人類免疫缺陷病毒/丙型肝炎病毒合併感染者的血漿IL-27濃度比健康參照組顯著地升高；人類免疫缺陷病毒單獨感染組中，血漿IL-27濃度與CD4⁺ T淋巴細胞數量顯著正相關。人類免疫缺陷病毒/丙型肝炎病毒合併感染組中，人類免疫缺陷病毒載量與血漿IL-27濃度顯著正相關 (r = 0.362, P = 0.049)。分析深圳男同性戀人群IL-27 p28基因的單核苷酸多態性，發現IL-27 p28 2905T/G 與人類免疫缺陷病毒感染相關，GGG單型可降低男同性戀人群人類免疫缺陷病毒感染的風險。 / Human Immunodeficiency Virus (HIV) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS); HIV/AIDS caused 1.8 million deaths world-widely in 2010 and became a major global health challenge. HIV co-infections with Hepatitis B virus (HBV), Hepatitis C virus (HCV) are common and have emerged into new health problems with severe clinical consequences. Since the discovery of HIV, massive progress in understanding of the pathogen has been achieved. Due to the restriction of research model, how human immune system responds to HIV infection, particularly, to HBV or HCV co-infections is still worthy further elucidation. / A cohort study was first conducted in Shenzhen regarding the seroprevalence of HBV, HCV infections among HIV-infected population. Totally 914 HIV positive individuals were recruited in the study and tested for HBsAg and anti-HCV antibodies. The results showed a 10.9% (100/914) HIV/HBV co-infection rate, 14.6% (133/914) HIV/HCV co-infection prevalence and 3.7% (34/914) HIV/HBV/HCV triple-infection prevalence. Multivariate logistic regression revealed that HIV transmission risk behavior was significantly associated with HIV, HBV, HCV co-infections. Most HIV/HBV co-infection cases got HIV through sexual contact including heterosexual and homosexual behaviors (95/100, 95%); while most HIV/HCV co-infection subjects were injection drug users (IDUs) (89/133, 66.9%). In the case of HIV/HBV/HCV triple-infection, IDUs accounted for a large ratio (28/34, 82.4%). Among IDUs, most of them were male (108/122, 88.5%) and nearly half were aged 27 to 32 years old (56/122, 45.9%). Near half people who got HIV through blood and blood products were HIV/HCV co-infected (10/23, 43.5%). Gender has a significant correlation with HIV risk behavior and most IDUs were male. / Next, we applied ELISA to test HIV positive clinical samples and proved that plasma interleukin-27 (IL-27) level was significantly elevated in HIV mono-infected, HIV/HBV co-infected and HIV/HCV co-infected subjects when compared with healthy controls. Later, we further revealed that plasma IL-27 titer was not significantly varied among HIV, HBV and HCV co-infections except between HIV/HCV co-infections and HIV/HBV/HCV triple-infections. We also observed a significant positive correlation between CD4⁺ T cell counts and plasma IL-27 titer within HIV mono-infected group (r = 0.177, P = 0.034). / We further analyzed the impact HIV and HCV viral loads on plasma IL-27 titer. We found there was no significant correlation between HIV viral load and IL-27 titer among HIV mono-infected individuals (r = - 0.063, P = 0.679); while a significant positive correlation was observed between HIV viral load and IL-27 titer in HIV/HCV co-infected individuals (r = 0.362, P = 0.049). In the case of HIV/HCV co-infection, there was no significant linear correlation between HIV and HCV viral loads (r = - 0.072, P = 0.704) but exist obvious subdivision of samples in terms of HIV and HCV viral loads with significant IL-27 titer variance (P = 0.014). No correlation was observed between HCV viral load and IL-27 titer (r = - 0.119, P = 0.530). / IL-27 p28 polymorphisms were genotyped with TaqMan® Allelic Discrimination Assay in Chinese men who have sex with men (MSM) population in Shenzhen and the results revealed that proportions of IL-27 p28 -964A/G and 4603G/A genotypes were not significantly different from the healthy controls; IL-27 p28 -964A/G and 4603G/A allele frequencies were similar between HIV positive MSM group and healthy control MSM group. Results also showed that for IL-27 p28 2905T/G polymorphism, TG genotype has a 2.77-fold decreased risk of HIV susceptibility and subjects with G allele has a 2.72-fold decreased risk of HIV susceptibility. Linkage disequilibrium (LD) coefficients were observed between IL-27 p28 -964A/G and 2905T/G ( / In conclusion, the seroprevalences of HBV and HCV infection among HIV positive population in Shenzhen were surveyed and risk factors associated with co-infections were analyzed. Plasma IL-27 titer was significantly elevated in HIV mono-infected, HIV/HBV co-infected and HIV/HCV co-infected individuals. IL-27 level was correlated with CD4⁺ T cell counts within HIV mono-infected people. A significant positive correlation was found between HIV viral load and IL-27 titer in HIV/HCV co-infected individuals (r = 0.362, P = 0.049). IL-27 p28 2905T/G was associated with individual susceptibility to HIV infection and haplotype GGG showed a protective role in restricting HIV infection in MSM population. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / He, Lai. / "October 2012." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 135-155). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / Abstract (English) --- p.iii / Abstract (Chinese) --- p.vi / Acknowledgements --- p.ix / Contents --- p.x / List of Tables --- p.xv / List of Figures --- p.xvi / Abbreviations --- p.xvii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Human Immunodeficiency Virus --- p.1 / Chapter 1.1.1 --- HIV virology --- p.1 / Chapter 1.1.1.1 --- HIV structure and genome organization --- p.1 / Chapter 1.1.1.2 --- HIV life cycle --- p.3 / Chapter 1.1.1.3 --- HIV genotypes --- p.5 / Chapter 1.1.2 --- HIV epidemiology --- p.6 / Chapter 1.1.2.1 --- Global HIV epidemiology --- p.6 / Chapter 1.1.2.2 --- HIV epidemiology in China --- p.9 / Chapter 1.1.3 --- HIV pathogenesis --- p.13 / Chapter 1.1.3.1 --- Natural history of HIV infection --- p.13 / Chapter 1.1.3.2 --- HIV transmission --- p.15 / Chapter 1.1.3.3 --- HIV tropism --- p.17 / Chapter 1.1.4 --- Immune responses to HIV infection --- p.19 / Chapter 1.1.4.1 --- Innate immune response --- p.19 / Chapter 1.1.4.2 --- Adaptive immune response --- p.21 / Chapter 1.1.5 --- Diagnosis --- p.24 / Chapter 1.1.6 --- HIV prevention --- p.25 / Chapter 1.1.7 --- Anti-HIV therapy --- p.25 / Chapter 1.1.8 --- Hepatitis B virus, Hepatitis C virus infection --- p.26 / Chapter 1.1.8.1 --- HBV infection natural history, diagnosis, disease progression and epidemiology --- p.26 / Chapter 1.1.8.2 --- HCV infection natural history, diagnosis, disease progression and epidemiology --- p.30 / Chapter 1.1.9 --- HIV, HBV, HCV co-infections --- p.32 / Chapter 1.2 --- Interleukin-27 --- p.36 / Chapter 1.2.1 --- Biology of IL-27 --- p.36 / Chapter 1.2.2 --- IL-27 on immune system --- p.37 / Chapter 1.2.3 --- IL-27 anti-tumor properties --- p.38 / Chapter 1.2.4 --- IL-27 antiviral features --- p.40 / Chapter 1.2.5 --- IL-27 with hepatitis --- p.41 / Chapter 1.3 --- Single-nucleotide polymorphisms (SNPs) --- p.42 / Chapter 1.3.1 --- Types of SNPs --- p.43 / Chapter 1.3.2 --- Functions of SNPs --- p.43 / Chapter 1.4 --- Objectives of the study --- p.45 / Chapter Chapter 2 --- Seroprevalence of HBV, HCV infection among HIV positive individuals in Shenzhen --- p.52 / Chapter 2.1 --- Introduction --- p.52 / Chapter 2.2 --- Materials and methods --- p.54 / Chapter 2.2.1 --- Study participants --- p.54 / Chapter 2.2.2 --- Measure of HBV, HCV seroprevalence --- p.55 / Chapter 2.2.3 --- Statistical analysis --- p.60 / Chapter 2.3 --- Results --- p.61 / Chapter 2.3.1 --- HIV infection in Shenzhen --- p.61 / Chapter 2.3.2 --- Seroprevalence of HBV, HCV infection among HIV positive individuals in Shenzhen --- p.61 / Chapter 2.4 --- Discussion --- p.65 / Chapter 2.4.1 --- HIV infection in Shenzhen --- p.65 / Chapter 2.4.2 --- HIV, HBV, HCV co-infections in Shenzhen --- p.68 / Chapter 2.4.3 --- Limitations of the study --- p.71 / Chapter Chapter 3 --- Upregulation of Interleukin-27 titer in HIV infected persons --- p.78 / Chapter 3.1 --- Introduction --- p.78 / Chapter 3.2 --- Materials and methods --- p.80 / Chapter 3.2.1 --- Study participants --- p.80 / Chapter 3.2.2 --- Measure of HIV, HBV, HCV infection --- p.80 / Chapter 3.2.3 --- Detection of IL-27 in plasma --- p.81 / Chapter 3.2.4 --- CD4 counting --- p.84 / Chapter 3.2.5 --- Statistical analysis --- p.84 / Chapter 3.3 --- Results --- p.84 / Chapter 3.3.1 --- Demographics of study participants --- p.84 / Chapter 3.3.2 --- Upregulation of IL-27 levels in HIV infected persons --- p.85 / Chapter 3.3.3 --- Correlation of plasma IL-27 titer with CD4⁺ T cell count --- p.86 / Chapter 3.4 --- Discussion --- p.86 / Chapter Chapter 4 --- Impact of HIV, HCV viral loads on Interleukin-27 titer among Antiretroviral Therapy- Naïve HIV positive Chinese --- p.95 / Chapter 4.1 --- Introduction --- p.95 / Chapter 4.2 --- Materials and methods --- p.96 / Chapter 4.2.1 --- Study participants --- p.97 / Chapter 4.2.2 --- HIV, HBV and HCV Serological assays --- p.97 / Chapter 4.2.3 --- CD4 counting --- p.97 / Chapter 4.2.4 --- Detection of plasma IL-27 --- p.98 / Chapter 4.2.5 --- Quantification of HIV, HCV viral loads --- p.98 / Chapter 4.2.6 --- Statistical analysis --- p.102 / Chapter 4.3 --- Results --- p.102 / Chapter 4.3.1 --- Demographics of study participants --- p.102 / Chapter 4.3.2 --- Plasma IL-27 was elevated in HIV-positive persons --- p.103 / Chapter 4.3.3 --- Correlation of IL-27 titer and CD4⁺ T cell count --- p.103 / Chapter 4.3.4 --- Correlation of HIV viral load and IL-27 titer --- p.104 / Chapter 4.3.5 --- Correlation of HCV viral load and IL-27 titer --- p.104 / Chapter 4.4 --- Discussion --- p.105 / Chapter Chapter 5 --- Association of Interleukin-27 polymorphisms with the susceptibility to HIV infection in a Chinese men who have sex with men population --- p.116 / Chapter 5.1 --- Introduction --- p.116 / Chapter 5.2 --- Materials and methods --- p.118 / Chapter 5.2.1 --- Study participants --- p.118 / Chapter 5.2.2 --- HIV screening --- p.118 / Chapter 5.2.3 --- Genomic DNA extraction --- p.119 / Chapter 5.2.4 --- IL-27 p28 -964A/G, 2905T/G and 4603G/A genotyping --- p.120 / Chapter 5.2.5 --- Statistical analysis --- p.121 / Chapter 5.3 --- Results --- p.122 / Chapter 5.3.1 --- Demographics of study participants --- p.122 / Chapter 5.3.2 --- IL-27 genotypes and allele frequencies in HIV MSM and healthy MSM controls --- p.122 / Chapter 5.3.3 --- LD analysis and haplotype analysis --- p.123 / Chapter 5.4 --- Discussion --- p.124 / Chapter Chapter 6 --- Summary and perspectives --- p.130 / Chapter 6.1 --- Summary --- p.130 / Chapter 6.2 --- Perspectives --- p.132 / Bibliography --- p.135