Ui M, Kuwata T, Igarashi T, Miyazaki Y, Tamaru K, Shimada T, Nakamura M, Uesaka H, Yamamoto H, Hayami M
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto, Japan.
J Med Primatol. 1999 Aug-Oct;28(4-5):242-8. doi: 10.1111/j.1600-0684.1999.tb00275.x.
We constructed three simian-human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity against challenge infection with gene-intact SHIV in rhesus macaques. Inoculation of SHIV-dn lacking nef and SHIV-drn lacking nef and vpr induced transient viremia, while that of SHIV-dxrn lacking nef, vpr, and vpx induced no viremia. The SHIVs with fewer deletions were more effective in inducing neutralizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene-intact SHIV-NM-3rN, all the SHIV-dn-vaccinated macaques and two of the four SHIV-drn-vaccinated macaques showed complete resistance. The other two SHIV-drn-vaccinated macaques and all SHIV-dxrn-vaccinated macaques did not show complete resistance, but they did show suppression of replication of the challenge virus. These results suggested that as more genes were deleted, protective immunity was decreased.
我们构建了三种缺乏调节基因的猿猴-人类免疫缺陷病毒(SHIV),并分析了它们在恒河猴中诱导针对基因完整的SHIV攻击感染的保护性免疫的情况。接种缺乏nef的SHIV-dn和缺乏nef及vpr的SHIV-drn会诱导短暂的病毒血症,而接种缺乏nef、vpr和vpx的SHIV-dxrn则不会诱导病毒血症。缺失较少基因的SHIV在诱导中和抗体和细胞毒性T淋巴细胞反应方面更有效。当这些恒河猴受到亲本基因完整的SHIV-NM-3rN攻击时,所有接种SHIV-dn的恒河猴以及四只接种SHIV-drn的恒河猴中的两只表现出完全抗性。另外两只接种SHIV-drn的恒河猴和所有接种SHIV-dxrn的恒河猴没有表现出完全抗性,但它们确实表现出对攻击病毒复制的抑制。这些结果表明,随着更多基因被删除,保护性免疫会降低。