Thompson Katherine A, Kent Stephen J, Gahan Michelle E, Purcell Damian F J, McLean Catriona A, Preiss Scott, Dale C Jane, Wesselingh Steven L
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
J Neurovirol. 2003 Aug;9(4):442-51. doi: 10.1080/13550280390218715.
Simian immunodeficiency virus (SIV) infection of macaques results in neurological abnormalities similar to those of human immunodeficiency virus (HIV)-associated dementia in humans and is a valuable system for the identification of viral neurotropic and neurovirulence factors. The authors recently established an SIV-macaque model where macaques can be infected with wild-type or nef/LTR-deleted SIVmac239 via administration of purified proviral DNA. In this study, the ability of wild-type and nef/LTR-deleted SIV infections to enter the cerebral spinal fluid (CSF) and brain was analyzed. In situ polymerase chain reaction (PCR) readily detected SIV gag DNA-positive cells in the mid-frontal gyrus and basal ganglia of the wild-type SIV-infected macaques, but not in nef/LTR-deleted SIV-infected or SIV-uninfected macaques. PCR on extracted DNA confirmed the in situ results, with multiple brain regions of the wild-type SIV-infected macaques positive for both gag and wild-type nef, whereas in the nef/LTR-deleted SIV-infected macaques, nef/LTR and gag DNA were undetectable. Further, macaques infected with nef/LTR-deleted SIV, which later became superinfected with wild-type SIV, also remained negative for SIV DNA in the brain by both in situ and extracted DNA techniques, despite having high levels of SIV RNA both in the CSF and plasma. This study provides evidence of the inability of nef/LTR-deleted SIV to initiate central nervous system (CNS) infection and suggests that, in the brain regions examined, nef/LTR-deleted viruses have either diminished neurotropism or insufficient systemic viral replication for entry into the CNS.
猕猴感染猿猴免疫缺陷病毒（SIV）会导致出现与人类免疫缺陷病毒（HIV）相关痴呆症类似的神经异常，是识别病毒嗜神经和神经毒力因子的宝贵系统。作者最近建立了一个SIV猕猴模型，通过给予纯化的前病毒DNA，猕猴可以感染野生型或缺失nef/LTR的SIVmac239。在本研究中，分析了野生型和缺失nef/LTR的SIV感染进入脑脊液（CSF）和大脑的能力。原位聚合酶链反应（PCR）很容易在野生型SIV感染猕猴的额中回和基底神经节中检测到SIV gag DNA阳性细胞，但在缺失nef/LTR的SIV感染或未感染SIV的猕猴中未检测到。对提取的DNA进行PCR证实了原位结果，野生型SIV感染猕猴的多个脑区gag和野生型nef均呈阳性，而在缺失nef/LTR的SIV感染猕猴中，未检测到nef/LTR和gag DNA。此外，感染了缺失nef/LTR的SIV、后来又被野生型SIV超感染的猕猴，尽管脑脊液和血浆中SIV RNA水平很高，但通过原位和提取DNA技术检测，其大脑中的SIV DNA仍为阴性。这项研究提供了证据，表明缺失nef/LTR的SIV无法引发中枢神经系统（CNS）感染，并表明在所检查的脑区中，缺失nef/LTR的病毒要么嗜神经能力减弱，要么全身病毒复制不足，无法进入中枢神经系统。
