The roles of endogenous retroviruses as cofactors of pathogenic retroviral infections

内源性逆转录病毒作为致病性逆转录病毒感染辅助因子的作用

• 批准号: 15580258
• 负责人: MIYAZAWA Takayuki
• 金额: $ 2.37万
• 依托单位: Obihiro University of Agriculture and Veterinary Medicine (2004)Osaka University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580258/
• 关键词: FeLV; endogenous retroviruses; FeLIX; Receptors; Pit1; AIDS; Cats; T lymphocytes; ネコ白血病ウイルス; 野生動物; ネコ科動物; 免疫不全; cDNAライブラリー; 発現クローニング

T-lymphotropic feline leukemia virus (FeLV-T) is a highly pathogenic variants of FeLVs, and induces feline AIDS (FAIDS) in cats. FeLV-T is fusion- defective because its PHQ motif, gammaretroviral consensus motif in the N-terminal regions of envelope protein, has substitution of histidine to aspartate. Infection of FeLV-T requires FeLIX, a truncated envelope protein encoded by an endogenous FeLV (enFeLV) for transactivation its infectivity and Pit1 for FeLIX-binding. Although Pit1 distributes in many cells, the expression of FeLIX is expressed only in some lymphoid organs. Therefore, it has been thought that the host cell range of FeLV-T is restricted to cells expressing FeLIX. However, because FeLIX is a soluble factor and expressed constantly, we presumed that FeLIX is present in blood and evaluated FeLIX activities in sera of various mammalian species by LacZ pseudotype assay. Here, we demonstrated that cat serum has FeLIX activity at functional level, suggesting that FeLIX is present abundantly in the internal environment of a cat and FeLV-T may be able to infect cells expressing Pit1 regardless FeLIX expression in vivo. We also confirmed that FeLIX did not inhibit FeLV-B infection despite FeLIX and FeLV-B exhibit the same receptor usage. These results implies that FeLIX may work just negatively for the host defence against the infection of exogenous viruses.

T淋巴细胞白血病病毒(FeLV-T)是猫T淋巴细胞白血病病毒(FeLV-T)的高致病变种，可引起猫艾滋病(FAIDS)。FeLV-T是融合缺陷的，因为它的PHQ基序，即位于包膜蛋白N-末端的伽马逆转录病毒共识基序，具有组氨酸替代天冬氨酸的作用。FeLV-T的感染需要由内源性FeLV(EnFeLV)编码的截短包膜蛋白Felix反式激活其感染性，需要Pit1与Felix结合。虽然Pit1分布在许多细胞中，但Felix的表达仅在某些淋巴器官中表达。因此，一直认为FeLV-T的宿主细胞范围仅限于表达Felix的细胞。然而，由于Felix是一种可溶性因子，并且不断表达，我们推测Felix存在于血液中，并通过LacZ假型试验评估了不同哺乳动物血清中Felix的活性。在这里，我们证明了猫血清在功能水平上具有Felix活性，这表明Felix大量存在于猫的内环境中，FeLV-T可能能够感染体内表达Pit1的细胞，而不考虑Felix的表达。我们还证实，尽管Felix和FeLV-B表现出相同的受体用途，但Felix并不抑制FeLV-B的感染。这些结果表明，Felix可能只对宿主防御外源病毒的感染起到负面作用。

项目成果

Y.Sakurai, T.Miyazawa et al.: "Identification of the feline CD53 homologue using retrovirus-mediated expression cloning"Veterinary Immunology and Immunopathology. 98. 185-191 (2004)

Y.Sakurai、T.Miyazawa 等人：“使用逆转录病毒介导的表达克隆鉴定猫 CD53 同源物”兽医免疫学和免疫病理学。

The Effect of Expression of Complement Regulatory Protein on Pig Endothelial Cells is Pig Endogenous Retrovirus (PERV) lyses by human sera.

补体调节蛋白表达对猪内皮细胞的影响是通过人血清裂解猪内源性逆转录病毒（PERV）。

• 发表时间: 2005
• 期刊: Transplant Proc. 37
• 作者: Hazama;K.;Miyagawa;S.;Yamamoto;A.;Kubo;T.;Miyazawa;T.;Tomonaga;K.;Watanabe;R.;Okumura;M.;Matsuda;H.;Shirakura;R.
• 通讯作者: R.

M.Shimojima, T.Miyazawa et al.: "Phenotypic changes in CD8+ peripheral blood lymphocytes in cats infected with feline immunodeficiency virus"Microbes and Infection. 5. 1171-1176 (2003)

M.Shimojima、T.Miyazawa 等人：“感染猫免疫缺陷病毒的猫 CD8 外周血淋巴细胞的表型变化”微生物与感染。

In vitro selective suppression of feline myeloid colony formation is attributable to molecularly cloned strain of feline leukemia virus with unique long terminal repeat

• DOI: 10.1016/j.rvsc.2004.07.003
• 发表时间: 2005-04-01
• 期刊: RESEARCH IN VETERINARY SCIENCE
• 影响因子: 2.4
• 作者: Nagashima, N;Hisasue, M;Hasegawa, A
• 通讯作者: Hasegawa, A

Cell-binding properties of the envelope proteins of porcine endogenous retroviruses.

• DOI: 10.1016/j.micinf.2005.01.008
• 发表时间: 2005-04
• 期刊: Microbes and infection
• 影响因子: 5.8
• 作者: R. Watanabe;T. Miyazawa;Y. Matsuura