Stephens E B, Sahni M, Leung K, Raghavan R, Joag S V, Narayan O
Department of Microbiology, Molecular Genetics and Immunology, Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, Kansas City 66160-7240, USA.
J Gen Virol. 1998 May;79 ( Pt 5):1089-100. doi: 10.1099/0022-1317-79-5-1089.
The question of whether consensus nucleotide substitutions in the long terminal repeat (LTR) region of simian immunodeficiency virus strain mac (SIVmac) are important for neurovirulence was investigated in this report. Brains and lymph nodes from two macaques that developed AIDS and encephalitis following inoculation with two strains of neurovirulent SIVmac, and from one animal with AIDS but no neurological disease after inoculation with non-neurovirulent SIVmac239 were used. The 5' LTR regions from neurovirulent SIVmacR71/17E and SIVmac7F-Lu were amplified, cloned and sequenced and these sequences were compared to the LTRs amplified from three regions of the respective encephalitic brains and lymph nodes from macaques inoculated with each virus. The SIVmac7F-Lu and SIVmacR71/17E viruses had zero and three consensus substitutions, respectively, in the U3, R and U5 regions of the LTR compared to that of SIVmac239. The only consensus substitution in the LTR-gag region of the genome was a T to C change at position 829 within the tRNA binding site. The sequences amplified from the brain and lymph nodes of the two animals with AIDS and encephalitis were identical. This single common substitution in this region of the virus genome, the T to C substitution at position 829, was also found in the LTRs isolated from the brain and lymphoid organs from the macaque inoculated with SIVmac239. The virtual identity in nucleotide sequences in the LTR of the neurovirulent and non-neurovirulent viruses and in CNS and lymph tissues of animals inoculated with the viruses suggests that the LTR has no effect on the tissue tropisms of the viruses.
本报告研究了猿猴免疫缺陷病毒株mac（SIVmac）长末端重复序列（LTR）区域的共有核苷酸替换对神经毒性是否重要。使用了两只猕猴的大脑和淋巴结，这两只猕猴在接种两株具有神经毒性的SIVmac后患上了艾滋病和脑炎，还使用了一只接种非神经毒性SIVmac239后患上艾滋病但无神经疾病的动物的大脑和淋巴结。对具有神经毒性的SIVmacR71/17E和SIVmac7F-Lu的5'LTR区域进行扩增、克隆和测序，并将这些序列与从接种每种病毒的猕猴相应脑炎大脑和淋巴结的三个区域扩增的LTR进行比较。与SIVmac239相比，SIVmac7F-Lu和SIVmacR71/17E病毒在LTR的U3、R和U5区域分别有零个和三个共有替换。基因组LTR-gag区域中唯一的共有替换是tRNA结合位点内第829位的T到C变化。从两只患有艾滋病和脑炎的动物的大脑和淋巴结中扩增的序列是相同的。在接种SIVmac239的猕猴的大脑和淋巴器官中分离的LTR中也发现了病毒基因组该区域的这一单一共同替换，即第829位的T到C替换。具有神经毒性和非神经毒性的病毒的LTR以及接种病毒的动物的中枢神经系统和淋巴组织中核苷酸序列的几乎完全相同表明，LTR对病毒的组织嗜性没有影响。
