Department of Mechanical, Aerospace and Biomedical Engineering, University of Tennessee, Knoxville, TN 37996, USA.
Bull Math Biol. 2011 Oct;73(10):2339-56. doi: 10.1007/s11538-010-9625-1. Epub 2011 Mar 4.
In this paper, we show how a game theoretic analysis can provide a model to explain the interdependence of host produced APOBEC3G levels and virus encoded Vif levels. We then use the relationship between these two opposing proteins in order to predict the success of two different HIV-1 viral variants, R5 and X4. From our analysis, we show that when APOBEC3G strongly favors mutation from an R5 strain to an X4 strain, it can be optimal for HIV-1 to suppress transmission of the X4 variant, despite the loss of X4 fitness potential. This is particularly true when the X4 strain significantly interferes with the host adaptive immune response, when Vif production is limited, or when host APOBEC3G targets the X4 strain more severely than the R5 strain. Using the proposed game theoretic analysis, we show that transmitting only R5 viruses has two advantages so far as HIV-1 is concerned. First, it allows for an increased R5 viral load due to immune interference caused by the X4 strain, and second, it forces the host to down-regulate APOBEC3G production, which is automatically favorable to the virus. APOBEC3G down-regulation, which is predicted in our model for a wide range of parameter values, may offer an explanation for the observed low level of APOBEC3G transcription and translation in hosts infected with HIV-1.
在本文中，我们展示了博弈论分析如何提供一个模型来解释宿主产生的 APOBEC3G 水平和病毒编码的 Vif 水平之间的相互依存关系。然后，我们利用这两种相反的蛋白质之间的关系来预测两种不同的 HIV-1 病毒变体 R5 和 X4 的成功。从我们的分析中可以看出，当 APOBEC3G 强烈有利于从 R5 株突变为 X4 株时，尽管 X4 株的适应性潜力丧失，但 HIV-1 抑制 X4 变体的传播可能是最佳选择。当 X4 株严重干扰宿主适应性免疫反应、Vif 产生受到限制，或宿主 APOBEC3G 对 X4 株的靶向性强于 R5 株时，这种情况尤其如此。通过提出的博弈论分析，我们表明，就 HIV-1 而言，只传播 R5 病毒有两个优势。首先，它允许由于 X4 株引起的免疫干扰而增加 R5 病毒载量，其次，它迫使宿主下调 APOBEC3G 的产生，这对病毒自动有利。我们的模型预测，在广泛的参数值范围内，APOBEC3G 的下调可能解释了在感染 HIV-1 的宿主中观察到的 APOBEC3G 转录和翻译水平低的现象。
