HIV-1gp41核心结构模拟位的筛选与鉴定

目的：筛选并鉴定HIV-1 gp4l核心表位。方法：用识别HIV-1 gp41的构象特异性单克隆抗体NC-1筛选噬菌体12肽库，通过夹心ELISA、NC-1特异性阻断实验、竞争抑制实验鉴定阳性噬菌体克隆，DNA序列分析阳性克隆。结果：经3轮筛选，随机挑取24个噬菌体克隆，ELISA鉴定表明有lO个克隆可与NC-1结合，DNA序列分析并推导氨基酸序列，共5种序列：HDVHHRWVYLLS、ITVNEWLYTSEQ、HGRSHGMFKPKR、MGPIARPHWHLN、DMYRSPRPKPDT。其中gp41N肽和C肽所形成的复合物可特异性阻断表达HDVHHRWVYLLS，VNEWLYTSEQ和MGPIARPHWHLN的克隆与NC-1的结合。结论：所得序列HDVHHRWVYLLS，VNEWLYTSEQ及MGPIARPHWHLN模拟HIV-1 gp41六螺旋束核心表位。     

Interleukin-6 and the IL-6 (–174) C/G polymorphism in breast pathologies and in HIV-infected patients

Introduction

Breast cancer and acquired immunodeficiency syndrome (AIDS) are key issues for modern medicine. The aim of the current study was to present how cytokines, in the example of IL-6 and its polymorphism, can affect these two conditions.

Material and methods

Thirty-one women with benign breast tumours, 42 breast cancer patients and 40 HIV-infected females were enrolled in the study. Serum IL-6 levels were determined by ELISA. The IL-6 polymorphism was genotyped by PCR-RFLP.

Results

Serum IL-6 in patients with benign breast tumours was significantly lower than in females with breast cancer (p = 0.017) and HIV-infected women (p = 0.032). We did not find statistically significant differences in serum IL-6 level between females with breast cancer and HIV-infected women (p = 0.749). Comparing the distribution of genotypes and frequency of the IL-6 (–174) C/G polymorphism between the three study groups – breast cancer patients, patients with benign breast tumours, and HIV-infected patients – we did not find any statistically significant differences.

Conclusions

IL-6 can play an important role in pathogenesis of breast cancer and HIV infection and its level is higher than in the control group irrespective of distribution of genotypes and frequency of the IL-6 (–174) C/G polymorphism.     

Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France

Although risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV‐genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV‐infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti‐HCV treatment who were referred to the 26 participating centers, 8.0% had severe liver disease, 25.7% were infected with HCV‐genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV‐genotype 3 (adjusted odds ratio, multiple imputation (aOR_MI) = 1.6, [95% confidence interval, 95% CI: 1.2–2.1]), HIV infection (aOR_MI = 1.8, [1.2–2.8]), male sex (aOR_MI = 2.0, [1.4–2.8]), age over 40 years (aOR_MI = 2.1, [1.6–2.9]), history of excessive alcohol consumption (aOR_MI = 2.8, [2.1–3.7]), and duration of infection ≥18 years (aOR_MI = 2.9, [2.0–4.3]). This analysis shows that HCV‐genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption, and co‐infection with HIV. These results are in favor of earlier treatment for drug users infected with HCV‐ genotype 3 and confirm the need for concomitant care for excessive alcohol consumption. J. Med. Virol. 82:1647–1654, 2010. 2010 Wiley‐Liss, Inc.     

Patterns of antibodies against latent and lytic antigens of human herpesvirus 8 in an endemic population and patients with Kaposi's sarcoma in Mozambique

The patterns of antibodies against latent and lytic antigens of human herpesvirus 8 (HHV‐8) were assessed using immunofluorescence assays of samples from 155 persons seropositive for HHV‐8 seen at public health centers and 24 patients with Kaposi's sarcoma (KS) from Mozambique. Of the 155 persons without KS, 48 (31%) had antibodies against latent antigens only, 29 (18.7%) had antibodies against lytic antigens only, and 78 (50.3%) had antibodies against both types of antigen. The HHV‐8 antibody titer tended to increase with age until age 40, after which it began to decrease. High titers of antibodies against latent and lytic antigens of HHV‐8 were detected mostly in persons co‐infected with HIV, and these increased titers could have a predictive value. All patients with KS except four patients who were seronegative for HHV‐8 had elevated titers of HHV‐8 antibodies, predominantly against latent antigens. The data suggest the potential for an increase in the development of KS in this endemic area for HHV‐8. J. Med. Virol. 82:1576–1581, 2010. © 2010 Wiley‐Liss, Inc.     

HIV疫苗研究进展

自上世纪80年代发现第一例艾滋病人以来,艾滋病发病率急剧上升,为了控制急剧上升的流行趋势,在20多年间,研究者们研发了数百种艾滋病疫苗,但疫苗临床试验几乎都以失败告终.直到2009年底,由赛诺菲-巴斯德公司(Sanofi-Pasteur)和瓦克斯根(VaxGen)公司合作的联合疫苗Ⅲ期临床试验才初见成效,这给艾滋病疫苗研究带来了希望.本文就较有潜力的艾滋病疫苗作用机制、研究策略以及临床试验进行综述,展望未来艾滋疫苗的研究方向.     

艾滋病相关工作人员焦虑情绪影响因素的对照分析

目的了解艾滋病相关工作人员心理焦虑状况及其影响因素,为其心理干预及制定心理卫生服务相关政策提供依据。方法对艾滋病相关工作人员进行一般状况问卷、症状自评量表(SCL-90)焦虑因子量表评定、艾滋病相关知识、HIV感染风险、艾滋病相关工作人员对同性恋和艾滋病预防措施态度问卷调查。并与其他疾病预防控制人员进行对照研究。结果1艾滋病相关工作人员的焦虑水平明显高于其他防疫人员,差异具有统计学意义(P0.05);2艾滋病相关工作人员与其他人群比较,对艾滋病治疗及服务态度肯定回答率和对同性恋态度肯定回答率差异具有统计学意义(P0.01);3影响焦虑情绪的危险因素有:害怕感染艾滋病(OR=1.027)、不能处理艾滋病心理问题(OR=1.039)及认为工作人员感染率高(OR=1.006)。保护性因素有得到官方告知(OR=0.009)、对同性恋持肯定态度(OR=0.909)及同情艾滋病患者(OR=0.196)。结论艾滋病相关工作人员的焦虑状况有待改善,积极对待艾滋病人及相关部门制定有力保护措施是可行之举。     

Rational approaches to immune regulation

Our laboratory is interested in the properties of proteins that render them immunogenic, and how such immunogenicity may be modulated in vivo. We are attempting to enhance the immune response in the design of more effective vaccines against viral diseases, such as HIV, and against tumor antigens expressed on breast, ovarian, and cervical cancer and B cell lymphomas. Our main approach is to use a facultative intracellular bacterium, Listeria monocytogenes, which has the unusual ability to live and grow in the cytoplasm of the cell and is thus an excellent vector for targeting passenger antigens to the major histocompatibility complex (MHC) class I pathway of antigen processing with the generation of authentic cytotoxic T lymphocytes (CTL) epitopes. In the field of tumor immunotherapy, we are also developing nonliving vaccine vectors for tumor antigens.