Multiple infection of target cells by human immunodeficiency virus (HIV) may lead to viral escape from host immune responses and drug resistance to antiretroviral therapy, bringing more challenges to the control of infection. The mechanisms underlying HIV multiple infection and their relative contributions are not fully understood. In this paper, we develop and analyze a mathematical model that includes sequential cell-free virus infection (i.e. one virus is transmitted each time in a sequential infection of target cells by virus) and cell-to-cell transmission (i.e. multiple viral genomes are transmitted simultaneously from infected to uninfected cells). By comparing model prediction with the distribution data of proviral genomes in HIV-infected spleen cells, we find that multiple infection can be well explained when the two modes of viral transmission are both included. Numerical simulation using the parameter estimates from data fitting shows that the majority of T cell infections are attributed to cell-to-cell transmission and this transmission mode also accounts for more than half of cell’s multiple infections. These results suggest that cell-to-cell transmission plays a critical role in forming HIV multiple infection and thus has important implications for HIV evolution and pathogenesis.

人类免疫缺陷病毒（HIV）对靶细胞的多次感染可能导致病毒从宿主免疫反应中逃脱，并对抗逆转录病毒疗法产生耐药性，这给控制感染带来了更多挑战。HIV多重感染的潜在机制及其相对作用尚不完全清楚。在本文中，我们开发并分析了一种数学模型，该模型包括顺序无细胞病毒感染（即在病毒对目标细胞的顺序感染中每次传播一种病毒）和细胞间传播（即多个病毒基因组是同时从感染细胞传播到未感染细胞）。通过将模型预测与HIV感染的脾细胞中原病毒基因组的分布数据进行比较，我们发现当同时包含两种病毒传播方式时，可以很好地解释多重感染。使用数据拟合中的参数估计值进行的数值模拟表明，大多数T细胞感染归因于细胞间传播，这种传播方式也占了细胞多次感染的一半以上。这些结果表明，细胞间传播在形成HIV多发感染中起着至关重要的作用，因此对HIV的进化和发病机理具有重要的意义。