Early detection of simian immunodeficiency virus in the central nervous system following oral administration to rhesus macaques.
Early detection of simian immunodeficiency virus in the central nervous system following oral administration to rhesus macaques.
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DOI：
10.3389/fimmu.2013.00236
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发表时间：
2013
影响因子：
7.3
通讯作者：
Sodora DL
中科院分区：
文献类型：
--
作者：
Milush JM;Chen HL;Atteberry G;Sodora DL
HIV传播到中枢神经系统（CNS）的时间可能对HIV疾病进展和治疗产生重要影响。HIV越早进入中枢神经系统，抗逆转录病毒治疗就越难清除。或者，HIV可能仅在疾病过程后期由于血脑屏障破坏而进入CNS。我们利用猴免疫缺陷病毒（SIV）感染的恒河猴，以评估在急性感染阶段的口服感染途径和随后的传播SIV的中枢神经系统。使用高剂量口服SIV攻毒以确保成功感染，并允许在感染后的前1-14天内评价CNS扩散。用超灵敏巢式PCR检测感染后1- 2d猕猴脑组织中SIV gagDNA，其中3例脑组织中检出SIV gagDNA。这种SIV DNA在猕猴大脑灌注后也存在，这提供了证据表明它不是驻留在循环血液中，而是驻留在脑组织本身中。病毒包膜V1-V2区在感染后早期的多样性表明，脑病毒变体与从淋巴结获得的变体相似。从淋巴组织和脑组织中获得的SIV之间的遗传相似性表明，病毒物种的创始人群体进入并随后传播，而没有任何脑特异性SIV选择的证据。SIV在经口传播后在CNS组织内相对快速的出现也可能发生在HIV传播期间，这可能影响疾病进程，并对长期治疗和未来的病毒根除模式构成挑战。
The timing of HIV dissemination to the central nervous system (CNS) has the potential to have important implications regarding HIV disease progression and treatment. The earlier HIV enters the CNS the more difficult it might be to remove with antiretroviral therapy. Alternatively, HIV may only enter the CNS later in the course of disease as a result of disruption of the blood-brain-barrier. We utilized the simian immunodeficiency virus (SIV) infection of rhesus macaques to evaluate the oral route of infection and the subsequent spread of SIV to the CNS during the acute infection phase. A high dose oral SIV challenge was utilized to ensure a successful infection and permit the evaluation of CNS spread during the first 1–14 days post-infection. Ultrasensitive nested PCR was used to detect SIV gag DNA in the brains of macaques at 1–2 days post-infection and identified SIV gag DNA in the brain tissues from three of four macaques. This SIV DNA was also present following perfusion of the macaque brains, providing evidence that it was not residing in the circulating blood but in the brain tissue itself. The diversity of the viral envelope V1–V2 region at early times post-infection indicated that the brain viral variants were similar to variants obtained from lymph nodes. This genetic similarity between SIV obtained from lymphoid and brain tissues suggests that the founder population of viral species entered and subsequently spread without any evidence of brain-specific SIV selection. The relatively rapid appearance of SIV within the CNS tissue following oral transmission may also occur during HIV transmission where it may impact disease course as well as representing a challenge for long-term therapies and future viral eradication modalities.
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DOI：
10.1056/nejmoa0911486
发表时间：
2010-06-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chasela CS;Hudgens MG;Jamieson DJ;Kayira D;Hosseinipour MC;Kourtis AP;Martinson F;Tegha G;Knight RJ;Ahmed YI;Kamwendo DD;Hoffman IF;Ellington SR;Kacheche Z;Soko A;Wiener JB;Fiscus SA;Kazembe P;Mofolo IA;Chigwenembe M;Sichali DS;van der Horst CM;BAN Study Group
通讯作者：
BAN Study Group
影响因子：
3.2
作者：
Lentz, Margaret R.;Kim, Woong-Ki;Gonzalez, R. G.
通讯作者：
Gonzalez, R. G.
影响因子：
9.9
作者：
Ellis, RJ;Gamst, AC;McCutchan, JA
通讯作者：
McCutchan, JA
影响因子：
5.4
作者：
DELWART, EL;SHEPPARD, HW;MULLINS, JI
通讯作者：
MULLINS, JI
影响因子：
6.4
作者：
Harrington, Patrick R.;Connell, Mary J.;Swanstrom, Ronald
通讯作者：
Swanstrom, Ronald