Molecular biological comparison of lntiviriruses isolated from animals.

本研究的目的是比较从不同动物中分离的慢病毒的分子生物学性质。在这些研究中，我们试图寻找在慢病毒中普遍观察到的遗传特性以及在分子水平上表达病毒在体内致病的机制。1)比较从日本、澳大利亚和美国分离的FIV毒株LtR的核苷酸序列，发现日本毒株与澳大利亚和美国的毒株有相当大的遗传差异。2)用嵌合LTR和嵌合FIV比较了两株不同毒株的生物学特性。虽然LTR的基本启动子活性没有差异，但病毒在CRFK细胞和MYA-1细胞中的有效生长受到Gag、Pol1、vif和ORF-A区的调控，而病毒对CRFK细胞的感染性和对MYA-1细胞的合胞体形成和细胞致病性的决定因素位于环境和REV区。3)通过ORF-A突变病毒，FIV ORF-A基因被发现有助于VIUS在已建立的T细胞系和外周血淋巴细胞中有效复制。4)FIV TM1毒株不能在表达CD4的猫CRFK细胞中复制，FIV env蛋白无法结合可溶性猫CD4。结果表明，FIV不利用猫科动物的CD4分子作为细胞感染的受体。

The purpose of the present studies is to compare the molecular biological nature of lentiviruese isolated from various animals. In these studies, we tried to find the genetic properities commonly observed among lentiviruese and the mechanisms for expression of pathogenesis of the viruses in vivo at a molecular level. We report here about feline immunodeficiency virus as a representative.1) When compared the nucleotide sequences of LTR of FIV isolated from Japan, Australia and U.S., Japanese isolates were considerable genetic devergence from both Australian and U.S.idolates. These results showed that FIV from Japan is phylogenetically distinct from those from the two countries.2) The biological proparities of two dofferent strains of FIV were compared by using chimeric LTR or chimeric FIV.Although there is no difference in the basal promoter activity of LTR, efficient viurs growth in CRFK cells and MYA-1 cells was found to be regulated by the gag, pol, vif and ORF-A regions, while viral determinants of infectivity for CRFK cells and syncytium formation and cytopathogenicity in MYA-1 cells were located in the env and rev regions.3) By using ORF-A mutant virus, the FIV ORF-A gene was found to facilitate efficient vius replication in established T-cell lines and peripheral blood lymphocytes.4) FIV TM1 strain could not replicate in feline CD4-expressing CRFK cells and FIV env protein fail to bind soluble feline CD4. The results indicate that FIV does not utilize feline CD4 molecule as a receptor for infection to the cells.