Molecular biological comparison of lntiviriruses isolated from animals.

本研究的目的是比较从各种动物中分离的慢病毒的分子生物学性质。在这些研究中，我们试图找到常见的慢病毒的遗传特性和在分子水平上表达的病毒在体内的致病机制。本文以猫免疫缺陷病毒为代表进行报道。1）比较了日本、澳大利亚和美国分离的猫免疫缺陷病毒LTR的核苷酸序列，日本的分离株是相当大的遗传偏差，从澳大利亚和美国的偶像。2）用嵌合LTR和嵌合FIV比较了两株FIV的生物学特性。虽然LTR的基础启动子活性没有差异，但发现病毒在CRFK细胞和MYA-1细胞中的有效生长受到gag、pol、vif和ORF-A区的调控，而病毒对CRFK细胞的感染性以及MYA-1细胞中合胞体形成和细胞致病性的决定因素位于env和rev区域。3）通过使用ORF-A突变病毒，发现FIV ORF-A基因促进了病毒在已建立T细胞系和外周血淋巴细胞中的有效复制。4）FIV TM 1株不能在猫CD 4-表达CRFK细胞和FIV env蛋白不能结合可溶性猫CD 4。结果表明，FIV不利用猫CD 4分子作为感染细胞的受体。

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.