Studies on receptors of animal lentiviruses

在动物中存在许多慢病毒，包括猫免疫缺陷病毒（FIV）和猿猴免疫缺陷病毒（SIV），并且在感染的动物中识别出各种症状，例如免疫缺陷综合征、脑炎和血液学病症。为了了解慢病毒感染动物的发病机制，研究病毒包膜与病毒受体之间的相互作用是非常重要的。本研究旨在分析FIV env基因的异质性及其致病潜力。首先，采用巢式PCR技术从患脑炎的猫的大脑、淋巴结和骨髓中扩增FIV env基因（V3-V6区），并测定其核苷酸序列。从这些组织中获得的15个病毒克隆由均匀的病毒群体组成，表明在这种情况下，来自单个克隆的病毒被传播。值得注意的是，该病例的病毒株（JN-BR 1株）与先前的日本分离株（TM 2株）显示出较低的序列相似性，但与显示出神经致病性的Petaluma株非常接近。第二，FIV env基因从显示骨髓抑制的猫的相同组织类似地扩增。从该病例的组织中获得的16个克隆在其氨基酸序列中观察到高达11.1%的显著遗传异质性。由于16个克隆中有5个在V3和V5区含有读框内终止密码子，因此认为它们是复制缺陷型的，并且与发病机制相关。虽然TM 2毒株已被证明属于亚型B，但发现来自该病例的病毒毒株（PTH-BM 3毒株）是包括几种致病性FIV的亚型A的成员。

There are a number of lentiviruses including feline immunodeficiency virus (FIV) and simian immunodeficiency virus (SIV) in animals, and various symptoms such as immunodeficiency syndrome, encephalitis and hematological disorders are recognized in the infected animals. To understand the pathogenesis by lentiviurs infection in animals, it is important to examine the interaction between virus envelope and virus receptor. In this year, our study was carried out to analyze the heterogeneity of FIV env gene and the pathogenic potential of the viruses. First, FIV env genes (V3-V6 region) were amplified by nested PCR from the cerebrum, lymph node and bone marrow of a cat with encephalitis, and the nucleotide sequences of these clones were determined. Fifteen viral clones obtained from these tissues were composed of a uniform viral population, indicating that viruses from a single clone were spread in this case. It was noteworthy that the virus strain from this case (JN-BR1 strain) showed a low sequence similarity with a previous Japanese isolate (TM2 strain), but was very close to Petaluma strain showing a neuropathogenicity. Second, FIV env genes were similarly amplified from the same tissues of a cat showing myelosupression. Marked genetic heterogeneity as high as 11.1% in their amino acid sequences was observed among the 16 clones from the tissues of this case. Since 5 of the 16 clones contained in-frame stop codons in the V3 and V5 regions, they were considered to be replication-defective and associated with the pathogenesis. Although the TM2 strain has been shown to belong to the subtype B,the virus strain from this case (PTH-BM3 strain) was found to be a member of subtype A which includes several pathogenic FIVs.