Chimeric simian and human immunodeficiency viruses (SHIVs) are appropriate animal models for the human immunodeficiency virus (HIV) because HIV has quite a narrow host range. Additionally, SHIVs that encode the HIV-1 Env protein and are infectious to macaques have many strains that show different pathogenesis, such as the highly pathogenic SHIV-KS661 and the less pathogenic SHIV-#64. Therefore, we used SHIVs to understand different aspects of AIDS pathogenesis. In a previous study, we established a mathematical model of in vivo early SHIV infection dynamics, which revealed the expected uninfected and infected dynamics in Rhesus macaques. In concrete, the number of uninfected CD4⁺ T cells in SHIV-KS661-infected Rhesus macaques decreased more significantly and rapidly than that of SHIV-#64 Rhesus macaques, and these Rhesus macaques did not any induce host immune response. In contrast, the number of uninfected CD4⁺ T cells in SHIV-#64-infected Rhesus macaques is maintained, and host immune response developed. Although we considered that the peak viral load might determine whether systemic CD4⁺ T cell depletion occurs or host immune responses develop, we could not investigate this because our model quantified only SHIV infection prior to the development of the pathogenicity or host immune responses. Therefore, we developed a new mathematical model to investigate why SHIV-#64 and SHIV-KS661 showed different long-term viral dynamics. We fitted our new model considering antibody responses to our experimental datasets that included antibody titers, CD4⁺ T cells, and viral load data. We performed a maximum likelihood estimation using a non-linear mixed effect model. From the results, we derived the basic reproduction numbers of SHIV-#64 and SHIV-KS661 from intravenous infection (IV) and SHIV-KS661 from intrarectal infection (IR), as well as the antiviral effects of antibodies against SHIV-#64(IV) and SHIV-KS661(IR). We found significant differences between the basic reproduction number of SHIV-#64(IV) or -KS661(IR) and that of SHIV-KS661(IV). We found no clear difference between the antiviral effects of SHIV-#64(IV) and SHIV-KS661(IR), and revealed that an antiviral effect more than 90% of that of maximum antibody responses was induced from initial antibody responses (i.e., antibody response just after its inducement). In conclusion, we found that the basic reproduction number, rather than SHIV strains determines whether systemic CD4⁺ T cell depletion develops, and the subsequent antibody responses occurs.

嵌合猿猴和人类免疫缺陷病毒（SHIV）是人类免疫缺陷病毒（HIV）的合适动物模型，因为HIV的宿主范围很窄。此外，编码HIV-1 Env蛋白并感染猕猴的SHIV具有许多表现出不同发病机理的菌株，例如高致病性SHIV-KS661和低致病性SHIV-＃64。因此，我们使用SHIV来了解AIDS发病机理的不同方面。在先前的研究中，我们建立了体内早期SHIV感染动力学的数学模型，该模型揭示了恒河猴的预期未感染和感染动力学。具体来说，未感染CD4 ⁺的数量感染SHIV-KS661的猕猴的T细胞比SHIV-＃64猕猴的T细胞下降更为明显和迅速，并且这些猕猴没有诱导宿主免疫反应。相反，在感染了SHIV-＃64的猕猴中未感染的CD4 ⁺ T细胞的数目得以维持，并且宿主免疫反应得以发展。尽管我们认为病毒载量峰值可能决定系统性CD4 ⁺发生T细胞耗竭或产生宿主免疫反应，我们无法对此进行调查，因为我们的模型仅在致病性或宿主免疫反应发生之前定量了SHIV感染。因此，我们开发了一个新的数学模型来研究SHIV-＃64和SHIV-KS661为什么表现出不同的长期病毒动力学。考虑到抗体对包括抗体效价，CD4 ⁺T细胞和病毒载量数据。我们使用非线性混合效应模型执行了最大似然估计。根据结果​​，我们推导了静脉感染（IV）的SHIV-＃64和SHIV-KS661的基本繁殖数，以及直肠内感染（IR）的SHIV-KS661的基本繁殖数，以及针对SHIV-＃64的抗体的抗病毒作用（ IV）和SHIV-KS661（IR）。我们发现SHIV-＃64（IV）或-KS661（IR）的基本繁殖数量与SHIV-KS661（IV）的基本繁殖数量之间存在显着差异。我们发现SHIV-＃64（IV）和SHIV-KS661（IR）的抗病毒作用之间没有明显差异，并且发现抗病毒作用是最大抗体反应的90％以上是由初始抗体反应诱导的（即，诱导后立即产生抗体应答）。总而言之，我们发现基本繁殖数，⁺ T细胞耗竭，随后发生抗体反应。