SIVcpz closely related to the ancestral HIV-1 is less or non-pathogenic to humans in a hu-BLT mouse model.
SIVcpz closely related to the ancestral HIV-1 is less or non-pathogenic to humans in a hu-BLT mouse model.
复制标题
DOI：
10.1038/s41426-018-0062-9
复制
发表时间：
2018-04-04
影响因子：
13.2
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yuan Z;Kang G;Daharsh L;Fan W;Li Q
HIV-1大流行是野生黑猩猩免疫缺陷病毒(SIVcpz)跨物种传播给人类的结果。我们先前的研究表明，与HIV-1组M组(SIVcpzMB897)和N组(SIVcpzEK505)的祖先病毒密切相关的SIVcpz毒株以及与人类任何已知HIV-1感染无关的两个SIVcpz谱系(SIVcpzMT145和SIVcpzBF1167)都可以很容易地感染并在人源化BLT小鼠模型中强劲复制。然而，不同SIVcpz毒株之间的比较致病性仍不清楚。在这里，我们用人源化的BLT小鼠比较了上述四株SIVcpz毒株与HIV-1的致病性。出乎意料的是，我们发现所有四个SIVcpz毒株与HIV-1相比，致病性或非致病性都明显较低，表现出较低的CD4+T细胞耗竭和免疫激活程度。对感染SIVcpz和HIV-1的Hu-BLT小鼠的CD4+T细胞的转录组分析显示，感染SIVcpz的小鼠与细胞生存相关的基因表达增强，炎症/免疫激活减少。总而言之，我们的研究结果首次表明，与HIV-1相比，SIVcpz对人类免疫细胞的致病性显著减少或非致病。我们的发现为可能对HIV-1进化起源的新理解奠定了基础，在这种情况下，最初的SIVcpz跨物种传播病毒最初对人类的致病性可能较低。
The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. Unexpectedly, we found that all four SIVcpz strains were significantly less pathogenic or non-pathogenic compared to HIV-1, manifesting lower degrees of CD4+ T-cell depletion and immune activation. Transcriptome analyses of CD4+ T cells from hu-BLT mice infected with SIVcpz versus HIV-1 revealed enhanced expression of genes related to cell survival and reduced inflammation/immune activation in SIVcpz-infected mice. Together, our study results demonstrate for the first time that SIVcpz is significantly less or non-pathogenic to human immune cells compared to HIV-1. Our findings lay the groundwork for a possible new understanding of the evolutionary origins of HIV-1, where the initial SIVcpz cross-species transmission virus may be initially less pathogenic to humans.
登录
查看更多内容
影响因子：
17.1
作者：
Muenchhoff M;Adland E;Karimanzira O;Crowther C;Pace M;Csala A;Leitman E;Moonsamy A;McGregor C;Hurst J;Groll A;Mori M;Sinmyee S;Thobakgale C;Tudor-Williams G;Prendergast AJ;Kloverpris H;Roider J;Leslie A;Shingadia D;Brits T;Daniels S;Frater J;Willberg CB;Walker BD;Ndung'u T;Jooste P;Moore PL;Morris L;Goulder P
通讯作者：
Goulder P
影响因子：
7.3
作者：
Gardino, Alexandra K.;Yaffe, Michael B.
通讯作者：
Yaffe, Michael B.
影响因子：
3.7
作者：
de Sousa, Joao Dinis;Mueller, Viktor;Vandamme, Anne-Mieke
通讯作者：
Vandamme, Anne-Mieke
影响因子：
5.3
作者：
Bleckmann, SC;Blendy, JA;Schütz, G
通讯作者：
Schütz, G
影响因子：
64.8
作者：
Li, QS;Duan, LJ;Haase, AT
通讯作者：
Haase, AT