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Studies On Association Between HIV-1 Biological Characteristics And Host Genetic Background With Disease Progression

Posted on:2004-03-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z R SunFull Text:PDF
GTID:1104360092995836Subject:Dermatology and Venereology
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IntroductionAIDS, which is called Acquired Immunodeficiency Syndrome, is a kind of immunodeficiency disease, Human Immunodeficiency Virus ( HIV) is the pathogen of AIDS. HIV can cause infected patients progressing to weakness of immune function and progressing to AIDS at last. Infected patients will die of opportunity infection and cancer. By now, HIV infection/AIDS cannot be cured completely or be prevented by any vaccine, because of the high variation rate of HIV gene. In the world there were 60 millions HIV -1 infected patients by the end of 2002, there were 24 millions HIV - 1 infected patients who died of AIDS. In China there were one million HIV - 1 infected patients by the end of 2002, when HIV infection and AIDS is in its fast increasing period. It is important to prevent and treat HIV infection effectively.Studies of large cohorts of HIV ?1 infected subjects have clearly indicated that the rate of progression of HIV disease may vary greatly among individuals, although most individuals infected with HIV developing AIDS within a median period of 10 years. Host and viral factors during HIV infection play a role in determining disease progression. Risk factors that influence the development of clinical disease and survival time of HIV - infected individual are poorly defined o The rate of CD4 + T lymphocyte counts declining and plasma HIV - 1 viral load increasing were considered prognostic indicators of AIDS progression. Simultaneously many studies showed: HIV -1 biological characteristics is an important factor which is correlated with disease progression in HIV - 1 infected patients. HIV - 1 biological phenotype and quasispecies diversity directly determined cellular tendency , mutant diversity and replication rate. In a word, HIVwith different characteristics influenced disease progression in vivo. So people pay more and more attention to the research of HIV -1 phenotype and quasispe-cies.HIV is transmitted by sexual behavior and transfusion , but not all the individuals exposed to HIV are infected and the disease course of infected individuals are obviously different. HLA ( Human leukocyte antigen) of host is an important factor of the susceptibility of HIV infection and disease progression. HLA is the main genetic mark of human and contains high polymorphism whose difference determines difference individual immune response. In nucleated cells and platelets, HLA class I genes encode molecules that present host or microbe - derived antigenic peptides to cytotoxic CDS -I- cells, which can attack and e-liminate the antigen - presenting cells.In the studies we have obtained 17 HIV -1 isolations by microseparation of the whole blood method and studied HIV -1 variation of biological characteristic , replication dynamic with disease progression, applied the HMA ( heterodu-plex mobility assay) to study the quasispecies variety of 48 HIV - 1 cases with disease progression, we have adopted PCR - SSP ( Polymerase chain reaction -sequence specific primer) to determine HLA - A, B, C alleles specificities of 46 cases Chinese HIV infected individuals and discussed the relationship between HIV infection and HLA.Materials and Methods1. Study subjectsHIV/AIDS patients were comfinned with HIV antibody positive (1-9 years without therapy) by the AIDS research center of China Medical University based on National AIDS examination protocol. All samples were collected before HAART. HIV/AIDS patients were divided into asymptomatic group ( CD4 + T cell>200/ul) and AIDS group (CD4 +T cell <200/ul) based on AIDS surveillance case definition for adolescents and adults.2. Virus isolation from 26 HIV/AIDS cases17 HIV - 1 isolations were obtained from 26 HIV/AIDS cases by microsep-aration of whole blood specimen method. The isolations were propagated and measured TCID50.3. Virus proliferation and Determination of NSI/SI phenotypeVirus HIV - 1 stocks to concentration of 100 TCID50 were added to the cultured macrophage at 5 × 105 cell/ml and MT - 2 cells at 2 × 105 cell/ml in 24 well micro...
Keywords/Search Tags:HIV-1, cell tropic, replication dynamics, quasispecies, HLA
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