4.4 Article

Modeling the role of macrophages in HIV persistence during antiretroviral therapy

期刊

JOURNAL OF MATHEMATICAL BIOLOGY
卷 81, 期 1, 页码 369-402

出版社

SPRINGER HEIDELBERG
DOI: 10.1007/s00285-020-01513-x

关键词

Viral infection model; Macrophages; Cell-to-cell transmission; Asymptotic analysis; HIV persistence

资金

  1. Postgraduate Research and Practice Innovation Program of Jiangsu Province [KYCX18_0375]
  2. NSFC [11671206, 11971232]
  3. CSC [201806840119]
  4. NSF [DMS-1758290]

向作者/读者索取更多资源

HIV preferentially infects activated CD4+ T cells. Current antiretroviral therapy cannot eradicate the virus. Viral infection of other cells such as macrophages may contribute to viral persistence during antiretroviral therapy. In addition to cell-free virus infection, macrophages can also get infected when engulfing infected CD4+ T cells as innate immune sentinels. How macrophages affect the dynamics of HIV infection remains unclear. In this paper, we develop an HIV model that includes the infection of CD4+ T cells and macrophages via cell-free virus infection and cell-to-cell viral transmission. We derive the basic reproduction number and obtain the local and global stability of the steady states. Sensitivity and viral dynamics simulations show that even when the infection of CD4+ T cells is completely blocked by therapy, virus can still persist and the steady-state viral load is not sensitive to the change of treatment efficacy. Analysis of the relative contributions to viral replication shows that cell-free virus infection leads to the majority of macrophage infection. Viral transmission from infected CD4+ T cells to macrophages during engulfment accounts for a small fraction of the macrophage infection and has a negligible effect on the total viral production. These results suggest that macrophage infection can be a source contributing to HIV persistence during suppressive therapy. Improving drug efficacies in heterogeneous target cells is crucial for achieving HIV eradication in infected individuals.

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