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Study Of The Function Of Ficolin-2 During HIV Infection And Epidemiological Survey Of HIV Co-infection

Posted on:2017-07-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:T L ChenFull Text:PDF
GTID:1364330512954942Subject:Immunology
Abstract/Summary:PDF Full Text Request
Part one Study of the function of ficolin-2 during HIV infectionBackground and objective:Ficolin-2, as a lectin complement pathway activator, is present in normal human plasma and usually associated with infectious diseases. Several reports have shown that ficoin-2 protein is dysfunctional or aberrantly expressed in some human serious infectious diseases. But little is known about the role of ficolin-2 in human immunodeficiency virus (HIV) infection. This study aims to study the function of ficolin-2 during HIV-1 infection.Methods:The sandwich ELISA was used to qualify the expression level of serum ficolin-2 protein in the 103 HIV-1 patients and 57 healthy donors. HEK293T cell was transfected with HIV-1 JRFL plasmid or HIV-1 pNL4-3 Luc R-E-plasmid, and qRT-PCR and western blot were used to detect the expression of ficolin-2 in HEK293T cell after transfection. Then GST pull-down and flow cytometry were used to detect the interaction between ficolin-2 and HIV-1 gp120. Finally, the effects of ficolin-2 on HIV-1 infection, CDC activation and HIV-1 pp infection were detected by Luciferase Assay.Results:Our results showed that serum ficolin-2 concentrations of 103 HIV-1 patients were much higher compared to those of 57 healthy donors. In vitro analysis showed that HIV-1 infection could enhance ficolin-2 protein expression. We further demonstrated that recombinant ficolin-2 protein could bind with HIV-1 envelope glycoprotein gp120, and subsequently induce complement dependent cytotoxicity. Moreover, ficolin-2 protein could block the entry and infection of HIV-1 into target cells (TZM-bl and MT-2 cells) in a ficolin-2 protein dose dependent manner.Conclusion:This is the first report that the serum ficolin-2 protein concentration is significantly increased in HIV patients. In addition, ficolin-2 protein can bind with HIV-1 envelope glycoprotein gp120 and neutralize and inhibit HIV-1 infection.Part two Epidemiological survey on HIV co-infection with HBV/HCVBackground and objective:HIV, HBV and HCV are three of the major pathogens of huamn infectious diseases which can lead to death. They share the same transmission pathway, which are all predominantly transmitted through sexual contact, transfusion of blood or blood materials and mother to child. This study aims to explore the epidemiological features of HIV and co-infection with HBV and HCV in patients with HIV infection.Methods:1618 HIV positive patients' clinical data were collected from the infectious department of Zhongnan hospital of Wuhan university during January 2011 to December 2015, then all data were divided into four groups:HIV group (patients only infected with HIV), HIV/HBV group (patients infected with HIV and HBV), HIV/HCV group (patients infected with HIV and HCV) and HIV/HBV/HCV (patients infected with HIV, HBV and HCV), and the epidemiological and clinical data of all patients in these four groups were conducted through retrospectively analysis.Results:The co-infection rates of HIV and HBV/HCV were 18.05% among 1618 HIV infections. Among them, co-infection rates of HBV, HCV and HBV and HCV were 8.96%,7.42% and 1.67%, respectively. HIV infection patients were predominantly male ranged from 21 to 60 years old, and the ratio of male to female was up to 2.5:1, but HIV/HCV co-infection patients were predominantly female, and HIV/HBV co-infection patients were predominantly male. Only HIV infection patients'numbers were increased but numbers of HIV co-infection with HBV or HCV were decreased year by year from 2011 to 2015. HIV and HIV/HBV were predominantly married, with the highest proportion of farmers; HIV and HIV/HBV were mainly transmitted through sex route, and HIV/HCV co-infection was mainly through blood transmission.91.16% of the HIV-infected patients were immunodeficient, and 68.97% of patients were with severe immunodeficiency (CD4+T cells?200/?l). The proportion of severe immunodeficiency was the highest when HIV co-infection with HBV (75.86%).Conclusion:Most of 1618 patients with HIV infection were male ranged from 21 to 60 years old, and most of them were married. They were mainly farmers, and sexual contact is the main transmission route. Most of them had severe immune deficiency. 8.96% HIV-infected patients were co-infected with HBV, which is more common than coinfection with HCV (7.42%). The sexual contact is the major transmission routes for only HIV-infected patients and HIV/HBV co-infected patients, but blood transmission is major for HIV co-infected with HCV. HIV co-infection with HBV is prone to severe immunosuppression (CD4+T cells?200/?l).Part three Epidemiological survey on HIV co-infection with TBBackground and objective:AIDS and TB are two major human chronic infectious diseases, which severely threat human health. One of the most common complications from acute HIV infection to AIDS is infection with Mycobacterium tuberculosis (MTB), which even lead to death. This study aims to explore the epidemiological features of HIV and its co-infection with MTB in patients with HIV infection.Methods:The clinical data of the 1618 patients with HIV infection were collected from the infectious department of Zhongnan hospital of Wuhan university during January 2011 to December 2015, then all patients were divided into two groups:HIV group (patients only infected with HIV), HIV/TB group (patients infected with HIV and TB), and the epidemiological and clinical data of all patients in these two groups were conducted retrospectively analysis.Results:The co-infection rate of HIV and TB was up to 20.27%(WHO 1/3), which was higher than the co-infection rate with HVB/HCV (18.05%).77.74% of HIV patients with TB had severe immunodeficiency (CD4+T cells?200/?l), which was significantly higher than HIV infection alone. HIV combined TB accounted for the largest age group ranged from 21 to 30 years old, which was tend to be younger than HIV infection only which largest age group ranged from 41 to 50 years old. HIV combined with TB patients were still predominately men, mainly in sexual transmission and farmers were major populations.Conclusion:The numbers of HIV patients co-infected with TB in hospital are increased year by year from 2011 to 2015. Among the HIV infected patients,20.27% of them were co-infected with MTB. Most of the HIV co-infection with TB are young people who were 21-30 years old. In addition,77.74% of HIV patients co-infected with TB were with severe immunosuppression (CD4+T cells?200/?l).
Keywords/Search Tags:ficolin-2, HIV, lectin complement pathway, innate immune molecule, HBV, HCV, co-infection, retrospectively analysis, MTB
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