期刊
JOURNAL OF THEORETICAL BIOLOGY
卷 509, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2020.110502
关键词
HIV infection; Mathematical model; Multiple infections; Cell-to-cell transmission; Sequential cell-free virus infection
资金
- NSFC [12071217, 11671206, 11971232]
- Postgraduate Research and Practice Innovation Program of Jiangsu Province [KYCX20_0243]
- CSC [201806840119]
- NSF [DMS-1758290, DMS-1950254]
The study suggests that including both sequential cell-free virus infection and cell-to-cell transmission can well explain HIV multiple infection. Numerical simulations show that the majority of T cell infections are attributed to cell-to-cell transmission, which also accounts for more than half of cell's multiple infections.
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. (C) 2020 Elsevier Ltd. All rights reserved.
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