肾综合症出血热的分子流行病学研究

用RT-PCR,限制性内切酶图谱分析及直接测序技术对来自湖北省同一肾综合症出血热(HFRS)疫区不同年代(1985至1988年),不同宿主(黑线姬鼠,褐家鼠与人)的汉坦病毒(HV)进行基因分型和核苷酸序列测定,确定HV在同一地区不同年代,不同宿主间的基因特征和变异规律,从而狧FRS流行的监测,HV疫苗的应用及HV致病机制的认识提供理论依据.

The prevalent law of hemorrhagic fever with renal syndrome (HFRS) is still unillustrated and.the epidemic situation can’t be controlled effectively.Since viral Rgenetic variation is of important.revelation for the solution of the problem, we try to clarify the relationship between HV diversity.and epidemic of HFRS by studying the law of HV variation.McAb is used to analyze the antigen.character of HV and RT-PCR,restriction map along with sequencing technology are employed to.assay HV strains obtained from different period (1985-2000) and different region in Hubei.The.results include:1)According to antigenicity, HV strains in Hubei can be divided into at least such.three types as HTN type, SEO type and a new type named unidentified type.Antigenic diversity is.observed between strains isolated from human and animal and manifests different reactivity to.McAb 25-1;2) 148 strains of HV collected from 1985 to 2000 in Hubei are analyzed by using.endonuclease AvaⅡ，DdeⅠand HinfⅠ.The result shows that viral genotype is accordant to.serotype. The restiction maps can be classfied as type A, B, C and D within which type A (same.as that of strains isolated 14 years ago) accounts for more than 63% in each period with relatively.steady genotype and no significant variation in five years.3)Using RT-semi nested PCR to.analyze 30 strains of HV from 6 counties in Hubei, we find Hubei province is the mixed epidemic.area where there maybe exist two types of virus in a same region.HTN genotype is unstable but.SEO genotype is steady.Viral variation has area collecticity;4)Phylogenetic tree analysis of.Hantaan virus Hubei strain After obtaining the genetic character of different period and different.region, we sequence parts of viral strains and find 3 strains whose homologies with HTN 76-118.are respectively 82%,83% and 83.3%; 1 strain’s homology with HTN 76-118 is 99%. Compared.国家自然科学基金资助项目结题报告.4.with the strain isolated 14 years ago, the homologies are respectively 95%,96%,96%,84%. We.also find a strain has base depletion in location 1490 which results in codon in site 486 and 489 of.protein G1 changing into termination codon. The discovery hints that, in Hubei, there are not only.strains in the same phylogenetic tree with HTN 76-118, but also strains in the same phylogenetic.tree with A9 and HV 114 isolated 14 years ago;5) This program fosters 8 graduates and doctors.altogether. Especially, we establish scientific research cooperationship and communication with.abroad and Taiwan through graduate culture.