Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.
Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1.
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DOI：
10.1084/jem.20082831
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发表时间：
2009-05-11
期刊：
影响因子：
--
通讯作者：
Shaw GM
中科院分区：
文献类型：
--
作者：
Keele BF;Li H;Learn GH;Hraber P;Giorgi EE;Grayson T;Sun C;Chen Y;Yeh WW;Letvin NL;Mascola JR;Nabel GJ;Haynes BF;Bhattacharya T;Perelson AS;Korber BT;Hahn BH;Shaw GM
我们最近开发了一种新的策略，使用单基因组扩增和随机病毒进化模型来识别在急性感染的人类中传播的HIV-1基因组。在这里，我们使用这种方法来确定猴免疫缺陷病毒(SIV)在18只实验感染的印度恒河猴中传播的分子特征。动物经直肠接种(ir.)或静脉注射(Iv)具有表现出早期-慢性HIV-1感染典型的序列多样性的SIVmac251或SIVsmE660的库存。从感染后1-5wk的血浆病毒粒子RNA中测定987个全长SIV env序列(每只动物中位数为48个)。红外线。接种之后是一种或几种病毒的生产性感染(中位数1；范围1-5)，这些病毒随机变化，具有接近星形的系统发育和泊松分布的突变。增强型和高峰期病毒血症的普遍病毒序列与接种物中发现的病毒相同，或仅有一个或几个核苷酸不同，提供了早期血浆病毒序列合并为传播/创始病毒的直接证据。静脉注射。感染的效率是I.R的2000倍。感染，通过两种途径传播的病毒代表了接种物的全部遗传谱。这些发现确定了SIV和HIV-1在粘膜传播和早期多样化方面的关键相似之处，从而验证了用于HIV-1疫苗和杀微生物剂研究的SIV-猕猴粘膜感染模型。
We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1–5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1–5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV–macaque mucosal infection model for HIV-1 vaccine and microbicide research.
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影响因子：
32.4
作者：
Hladik, Florian;Sakchalathorn, Polachai;Ballweber, Lamar;Lentz, Gretchen;Fialkow, Michael;Eschenbach, David;McElrath, M. Juliana
通讯作者：
McElrath, M. Juliana
影响因子：
5.4
作者：
Ma, ZM;Abel, K;Miller, CJ
通讯作者：
Miller, CJ
影响因子：
5.8
作者：
Maydt, J;Lengauer, T
通讯作者：
Lengauer, T
DOI：
10.1073/pnas.95.15.8869
发表时间：
1998-07-21
影响因子：
11.1
作者：
Chun, TW;Engel, D;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
6.4
作者：
Grobler, J;Gray, CM;Williamson, C
通讯作者：
Williamson, C