丙型肝炎病毒感染机制的研究进展

丙型肝炎病毒感染的机制目前尚不明了,大量的证据表明CD81是该病毒感染的最初受体,也有实验认为病毒与低密度脂蛋白结合后通过低密度脂蛋白受体的介导进入细胞。本文对该病毒感染的受体及它们的多态性研究作一综述。

出血热病毒感染机制

据美国BIOCOMPARE科技新闻网（2007／2／26）报道，2月7日发表于《自然》（Nature）期刊中的一项研究称，美国波士顿儿童医疗中心肺疾病分部的Hyeryun Choe博士与哈佛医学院的Michael Farzan博士，发现能够引起致命出血热的新世界沙状病毒（New World arenaviruses）感染途径。

艾滋病和埃博拉病毒感染机制揭开

英国利兹大学领导的一个研究团队日前首次观察到艾滋病病毒和埃博拉病毒如何附着于细胞并传播病毒感染。这项发表在《应用化学》杂志上的最新成果有望为治疗这些疾病提供新的方法：阻断病毒与细胞之间的互动，而不是消灭病原体。

研究鱼类模式识别受体抗病毒感染机制

RIG—I样受体（RLRs）是一类新发现的模式识别受体，能够识别细胞质中的病毒RNA，在抗病毒天然免疫中起着重要的作用。RIG—I样受体包括视黄酸诱导基因I（RIG-1）、黑色素瘤分化相关基因5（MDA5）以及LGP2。

日发现一种白血病病毒感染机制

据新华社报道，京都大学2015年2月5日发表一份公报称，该校研究人员发现一种白血病病毒的感染机制，这将有助于将来研发出相关治疗方法。 人类T淋巴细胞白血病病毒Ⅰ型（HTLV-1）只感染成熟T淋巴细胞。研究人员分析后发现，在感染的细胞内，有两种蛋白质的表达显著减少，而这两种蛋白质能够发挥阻碍HTLV-1复制的作用。研究人员认为，由于这两种蛋白质在胸腺的未成熟T淋巴细胞内高度表达，但是在末梢的成熟T淋巴细胞内表达则很低，因此HTLV-1才会把成熟的T淋巴细胞作为感染的目标。

肾移植受者的巨细胞病毒和多瘤病毒感染

美国马萨诸塞州波士顿医院的Robert H．Rubin博士通过对巨细胞病毒（CMV）和多瘤病毒感染机制的描述，解释了肾移植术后常见的感染模式。移植术后的感染风险可由4种因素的共同作用所致：1）解剖学或技术性“意外”，如吻合口漏；2）免疫抑制水平异常；3）流行病学或环境暴露；4）通过进化或选择而耐药的病毒。尽管免疫抑制治疗及抗微生物治疗取得显著进展，但数年前由Rubin博士提出的移植术后感染的时间窗仍然未发生明显改变，有关时间窗的确定将有助于临床医生在移植患者出现感染时进行鉴别诊断。

基于病毒猴群算法的传感器优化布置方法研究

将病毒进化理论引入到猴群算法中,提出了一种用于传感器优化布置的病毒猴群算法。采用双重编码的方式,克服了原猴群算法只能解决连续变量优化问题的缺陷;在猴群中引入生物病毒机制对其进行感染,通过病毒和猴群的分工协作,来实现猴群个体之间纵向和横向的信息交流,以此维持个体的多样性,来大幅度增强算法的局部搜索能力;并将猴群不断的进行分类,采用大病毒和小病毒分别对其进行感染操作,加强算法的搜索精度。文末以大连国贸大厦为例,进行了参数敏感性分析以及传感器优化布置方案的选择,结果表明,病毒猴群算法的搜索效率较原猴群算法有了大幅提高,能较好地解决传感器优化布置问题。

一种清除“1465”病毒的方法

一种清除“１４６５”病毒的方法人民银行湖南省分行唐祖华“１４６５”病毒是国内近来发现的一种典型文件型病毒。因将被感染文件的长度增加１４６５个字节而得名。笔者通过对被该病毒感染文件的分析，获得了该病毒的表现特征及其感染机制，得到了一种清除该病毒的方法。...

两个人类基因与感染禽流感有关

美国芝加哥大学一个科研团队发现，H5N1禽流感病毒感染人类肺上皮细胞的机制与两个人类基因有关，因此可以通过影响这两个基因来开发抗病毒的新方法。相关论文近期发表在新一期美国学术刊物《细胞报告》上。研究人员说，H5N1禽流感病毒感染人体时，常通过肺上皮细胞入侵。为了筛查哪些基因与病毒感染机制有关，研究人员利用基因编辑技术制造出约1．9万个存在不同基因变异的肺上皮细胞，让它们接触H5N1病毒。

Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells

AIM： To investigate the effect of the serum of patients with chronic hepatitis B （CHB） on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus （HBV） and transforming growth factor-β1 （TGF-β1） in the pathogenesis of hepatitis B virus associated glomerulonephritis （HBV-GN）. METHODS： The levels of serum TGF-β1 were measured by specific enzyme linked immunosorbent assay （ELISA） and HBV DNA was tested by polymerase chain reaction （PCR） in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell （HK-2） was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative（20 cases） and HBV-DNA positive （24 cases） for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer. RESULTS： The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01±5.85% and 17.58±8.35%, HBV DNA negative serum group 8.12±2.80% and 6.96 ± 2.76% than those in control group 4.25±0.65% and 2.33 ± 1.09%, respectively （P 〈 0.01）. The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum （P 〈 0.01）. Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA （r = 0.657）. The level of serum TGF-β1 in CHB group was 163.05 ± 91.35 μg/L, signifi- cantly higher as compared with 81.40 ± 40.75 μg/L in the control group （P 〈 0.01）.CONCLUSION： The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-β1 may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.

Analyses of prognostic indices of chronic liver failure caused by hepatitis virus

AIM: To analyze the related indices about the prognoses of chronic liver failure caused by hepatitis virus. METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P=1/(1+e^(-y)) (y=1.7262-0.0948X_1+2.9846X_2+0.6992X_3+1.6019X_4+2.0398X_5). (Note: X_1-Prothrombin activity; X_2-digestive tract hemorrhage; X_3-hepatic encephalopathy; A_4-hepatorenal syndrome; X_5-pulmonary infection.). CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.

Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: A pilot study

AIM： TO evaluate the safety and efficacy of chronic administration of Iosartan on hepatic fibrosis in chronic hepatitis C patients.METHODS： Fourteen patients with chronic hepatitis C non-responders （n = 10）, with contraindications （n = 2） or lack of compliance （n = 2） to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after Iosartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies （interval 6-14 mo）. Histological activity index （HAI） with fibrosis stage was assessed under blind conditions by means of Ishak＇s score. Subendothelial fibrosis was evaluated by digital image analyses.RESULTS： The changes in the fibrosis stage were significantly different between Iosartan group （decrease of 0.5±1.3） and controls （increase of 0.89±1.27; P〈0.03）. In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients （P〈0.04）. A decrease in sub-endothelial fibrosis was observed in the Iosartan group. No differences were found in HAI after Iosartan administration. Acute and chronic decreases in systolic arterial pressures （P〈0.05） were observed after the Iosartan administration, without changes in mean arterial pressure or renal function.CONCLUSION： Chronic AT-Ⅱ type 1 receptor （AT1R） blockade may reduce liver fibrosis in patients with chronic hepatitis C.

Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.CONCLUSION: T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.

An Overview of the Highly Pathogenic H5N1 Influenza Virus

Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. This review summarizes the current understanding of, and recent research on, the avian influenza H5N1 virus, including transmission, virulence, pathogenesis, clinical characteristics, treatment and prevention.

Circulating adhesion molecules in patients with virus-related chronic diseases of the liver

AIM: In the inflammatory state, intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) play a key role in promoting migration of immunological cells from the circulation to target site.Aim of our study was to investigate soluble forms of these molecules in patients with virus-related chronic liver diseases, to assess their behavior in different pathologies and correlation with severity of liver damage.METHODS: Circulating ICAM-1 and VCAM-1 were assayed by EIA commercial kits (R&D System Co.,Abington, UK) in 23 patients with chronic active hepatitis (CH), 50 subjects affected by liver cirrhosis (LC) and 15 healthy controls comparable for sex and age. In patients, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected by autoanalyzer.RESULTS: LC patients had significantly higher ICAM-1 values than CH patients (38.56±7.4 ng/mL vs 20.89±6.42 ng/mL; P＜0.001) and these ones had significantly higher values than controls (12.92±1.08 ng/mL; P＜0.001). In CH group, ICAM-1 levels were significantly related to inflammatory activity (P= 0.041) and ALT values (r= 0.77;P＜0.05). VCAM-1 values were significantly increased only in LC patients (P＜0.001) and related to severity of liver impairment.CONCLUSION: These findings suggest that the determination of serum ICAM-1 can be considered as an additional useful marker of hepatocellular necrosis and inflammatory activity in chronic hepatitis, while serum VCAM-1 is an indicator of liver fibrogenesis and severity of disease in cirrhosis.

Occult hepatitis B virus infection and cryptogenic chronic hepatitis in an area with intermediate prevalence of HBV infection

AIM： To assess the possible role of occult HBV infection in the pathogenesis of chronic hepatitis in Iranian patients. METHODS： After exclusion of autoimmune, metabolic and viral etiologies, 104 consecutive adult patients with histologic and biochemical features of chronic hepatitis and negative HBsAg were enrolled in the study. Qualitative PCR with a sensitivity of 150 × 10^3 copies/L, using two primers for Pre-S and core regions was applied to measure presence of HBV DNA in serum of the patients. RESULTS： All 104 patients completed the study Qualitative HBV DNA was positive in two patients （1.9%） CONCLUSION： Occult HBV infection has negligible role in the pathogenesis of cryptogenic chronic hepatitis in Iranian patients.

AIDS and associated malignancies

AIDS associated malignancies （ARL） is a major complication associated with AIDS patients upon irnmunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy （ARV）, the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi＇s sarcoma （KS）, Hodgkin＇s disease （HD） and non-Hodgkin＇s lymphoma （NHL）. The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV- 1 seronegative patients. For example nearly haft of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus （EBV） or human herpesvirus-8 （HHV-8）/Kaposi＇s sarcoma associated herpesvirus （KSHV）. The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (≤2 years) and late phase (＞2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed.RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which 'HBsAg, HBeAb, HBcAb' positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P＜0.05).CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma denovo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.