Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, MA, USA.
Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, MA, USA; St. Georges University of London, London, UK.
Cell Rep. 2018 Aug 21;24(8):2088-2100. doi: 10.1016/j.celrep.2018.07.079.
HIV-1 is transmitted between T cells through the release of cell-free particles and through cell-cell contact. Cell-to-cell transmission is more efficient than cell-free virus transmission, mediates resistance to immune responses, and facilitates the spread of virus among T cells. However, whether HIV cell-to-cell transmission influences the establishment of HIV-1 latency has not been carefully explored. We developed an HIV-1 latency model based on the transmission of HIV-1 directly to resting CD4+ T cells by cell-cell contact. This model recapitulates the spread of HIV-1 in T-cell-dense anatomical compartments. We demonstrate that productively infected activated CD4+ T cells transmit HIV-1 to resting CD4+ T cells in a cell-contact-dependent manner. However, proviruses generated in this fashion are more difficult to induce compared to proviruses generated by cell-free infection, suggesting that cell-to-cell transmission influences the establishment and maintenance of latent infection in resting CD4+ T cells.
HIV-1 通过释放无细胞颗粒和细胞间接触在 T 细胞之间传播。细胞间传播比无细胞病毒传播更有效，介导对免疫反应的抗性，并促进病毒在 T 细胞之间的传播。然而，HIV 细胞间传播是否影响 HIV-1 潜伏期的建立尚未得到仔细探讨。我们开发了一种基于 HIV-1 通过细胞间接触直接传播到静止 CD4+ T 细胞的 HIV-1 潜伏期模型。该模型再现了 HIV-1 在 T 细胞密集解剖隔室中的传播。我们证明，受感染的激活 CD4+ T 细胞以细胞接触依赖的方式将 HIV-1 传播到静止 CD4+ T 细胞。然而，与无细胞感染产生的前病毒相比，以这种方式产生的前病毒更难诱导，这表明细胞间传播会影响潜伏感染在静止 CD4+ T 细胞中的建立和维持。
