Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection.
Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection.
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干扰素-α对无细胞和细胞对HIV-1感染的反对作用。
DOI：
10.1371/journal.pcbi.1010053
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发表时间：
2022-04
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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在HIV-1感染者中，传播/创始者（TF）病毒有助于建立新的感染，并在感染的急性期扩大，而慢性控制（CC）病毒在感染的慢性期出现。TF病毒比CC病毒对干扰素-α（IFN-α）介导的抗病毒作用更具抗性，然而，其在感染个体中的病毒学相关性仍不清楚。在这里，我们进行了一个实验-数学调查，并显示，IFN-α强烈抑制CC病毒的细胞间感染，但只有微弱的影响，TF病毒。令人惊讶的是，IFN-α以病毒-细胞密度依赖性方式增强HIV-1的无细胞感染，特别是CC病毒的无细胞感染。我们进一步证明，LY 6 E，IFN-刺激的基因，可以有助于密度依赖性增强无细胞HIV-1感染。总之，我们的研究结果表明，TF和CC病毒之间的主要差异可以通过它们对IFN-α介导的细胞间感染抑制的抗性和它们对IFN-α介导的无细胞感染增强的敏感性来解释。HIV-1在传播过程中经历了一个强大的瓶颈，只有对宿主先天免疫具有较高抗性的病毒干扰素（IFN）才能成功传播。由于IFN抗性在感染个体的感染过程中趋于消失，因此这种表型对于人传人至关重要。通过数学建模和精心设计的时间序列病毒感染实验相结合的方法，研究了急性期和慢性期分离的两种HIV-1对IFN抗性的差异，并将其分为无细胞和细胞间感染两种病毒传播模式。我们发现IFN抑制HIV-1细胞间感染，但令人惊讶的是，促进无细胞感染。此外，在慢性感染期间分离的病毒比在急性感染期间分离的病毒对IFN介导的促进作用更敏感。我们的研究结果表明，HIV-1选择不同的策略来适应不同的宿主环境。我们进一步提供了病毒如何进化以抵消或劫持宿主免疫力的见解。
In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection. HIV-1 experiences a strong bottleneck during transmission, and only the virus(es) with higher resistance to the host’s innate immunity, interferon (IFN), can be successfully transmitted. Because the IFN resistance tends to be disappeared during infection in infected individuals, this phenotype would be crucial for human-to-human transmission. By combining mathematical modeling with well-designed time-series viral infection experiments, we investigated the difference on the IFN resistance of two types of HIV-1, which were respectively isolated at the acute and chronic phases of infection, and classified it into two virus transmission modes, cell-free and cell-to-cell infections. We found that IFN suppresses HIV-1 cell-to-cell infection, but surprisingly, promotes cell-free infection. Moreover, the virus isolated during chronic infection is more sensitive to the IFN-mediated promoting effect than that isolated during acute infection. Our results suggest that HIV-1 selects different strategies to adapt to different host environments. We further provide an insight how viruses evolve to counteract or hijack the host immunity.
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DOI：
10.1126/science.1254031
发表时间：
2014-07-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carlson JM;Schaefer M;Monaco DC;Batorsky R;Claiborne DT;Prince J;Deymier MJ;Ende ZS;Klatt NR;DeZiel CE;Lin TH;Peng J;Seese AM;Shapiro R;Frater J;Ndung'u T;Tang J;Goepfert P;Gilmour J;Price MA;Kilembe W;Heckerman D;Goulder PJ;Allen TM;Allen S;Hunter E
通讯作者：
Hunter E
影响因子：
8
作者：
Cheng, Liang;Yu, Haisheng;Su, Lishan
通讯作者：
Su, Lishan
影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
影响因子：
3.7
作者：
Browne, Edward P.;Letham, Benjamin;Rudin, Cynthia
通讯作者：
Rudin, Cynthia
影响因子：
5.4
作者：
Dixit, NM;Perelson, AS
通讯作者：
Perelson, AS