Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection.
Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection.
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DOI：
10.1371/journal.pone.0113691
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
daSilva LL
中科院分区：
文献类型：
--
作者：
de Carvalho JV;de Castro RO;da Silva EZ;Silveira PP;da Silva-Januário ME;Arruda E;Jamur MC;Oliver C;Aguiar RS;daSilva LL
Nef是一种HIV-1辅助蛋白，可促进病毒复制和致病。Nef的一个关键功能是通过诱导这些蛋白质靶向多泡体（MVB）并最终靶向溶酶体降解来确保感染细胞中CD 4和MHC-I分子的持续消耗。Nef还影响细胞分泌途径，通过外泌体促进其自身的分泌。为了更好地理解Nef对外泌途径的影响，我们研究了这种病毒因子是否改变了T淋巴细胞释放的外泌体的组成。我们表明，CD 4和MHC-I分子都分泌在T细胞的外泌体中，Nef的表达减少了外泌体中这些蛋白质的量。为了研究Nef这种新活性的功能作用，我们在不同外来体群体存在下进行了体外HIV-1感染测定。我们证明了由CD 4 + T细胞而不是CD 4 − T细胞释放的外泌体在体外有效抑制HIV-1感染。由于CD 4是HIV-1感染的主要受体，这些结果表明，外泌体表面展示的CD 4分子可以与HIV-1的包膜蛋白结合，阻碍病毒与靶细胞的相互作用和感染。重要的是，由表达Nef的CD 4 + T细胞释放的CD 4耗尽的外泌体在体外抑制HIV-1感染的能力降低。这些结果提供了证据表明，除了Nef降低细胞表面CD 4水平的原始作用外，Nef还通过降低来自感染细胞的外来体中CD 4的表达来促进HIV-1感染。
Nef is an HIV-1 accessory protein that promotes viral replication and pathogenesis. A key function of Nef is to ensure sustained depletion of CD4 and MHC-I molecules in infected cells by inducing targeting of these proteins to multivesicular bodies (MVBs), and ultimately to lysosomes for degradation. Nef also affects cellular secretory routes promoting its own secretion via exosomes. To better understand the effects of Nef on the exocytic pathway, we investigated whether this viral factor modifies the composition of exosomes released by T lymphocytes. We showed that both CD4 and MHC-I molecules are secreted in exosomes from T cells and that the expression of Nef reduces the amount of these proteins in exosomes. To investigate the functional role for this novel activity of Nef, we performed in vitro HIV-1 infection assays in the presence of distinct populations of exosomes. We demonstrated that exosomes released by CD4+ T cells, but not CD4− T cells, efficiently inhibit HIV-1 infection in vitro. Because CD4 is the main receptor for HIV-1 infection, these results suggest that CD4 molecules displayed on the surface of exosomes can bind to envelope proteins of HIV-1 hindering virus interaction with target cells and infection. Importantly, CD4-depleted exosomes released by CD4+ T cells expressing Nef have a reduced capacity to inhibit HIV-1 infection in vitro. These results provide evidence that Nef promotes HIV-1 infection by reducing the expression of CD4 in exosomes from infected cells, besides the original role of Nef in reducing the CD4 levels at the cell surface.
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影响因子：
4.8
作者：
Aguiar, Renato S.;Lovsin, Nika;Peterlin, B. Matija
通讯作者：
Peterlin, B. Matija
影响因子：
5.4
作者：
ANDERSON, SJ;LENBURG, M;GARCIA, JV
通讯作者：
GARCIA, JV
影响因子：
56.9
作者：
DEACON, NJ;TSYKIN, A;MILLS, J
通讯作者：
MILLS, J
影响因子：
3.3
作者：
Costa LJ;Chen N;Lopes A;Aguiar RS;Tanuri A;Plemenitas A;Peterlin BM
通讯作者：
Peterlin BM
DOI：
10.1083/jcb.200508014
发表时间：
2006-03-13
期刊：
The Journal of cell biology
影响因子：
--
作者：
Booth AM;Fang Y;Fallon JK;Yang JM;Hildreth JE;Gould SJ
通讯作者：
Gould SJ