Mechanisms of HIV-1 cell-to-cell transmission and the establishment of the latent reservoir

•HIV-1 utilizes several forms of cell-to-cell transmission that influence viral dissemination, survival and pathogenesis.•HIV-1 cell-to-cell transmission mediates the generation of latent infection in CD4 + T cells.•HIV-1 cell-to-cell transmission affects the regulation of HIV-1 latency, challenging the development of curative therapies. HIV-1 spreads through both the release of cell-free particles and by cell-to-cell transmission. Mounting evidence indicates that cell-to-cell transmission is more efficient than cell-free transmission of particles and likely influences the pathogenesis of HIV-1 infection. This mode of viral transmission also influences the generation and maintenance of the latent reservoir, which represents the main obstacle for curing the infection. In this review we will discuss general cell contact-dependent mechanisms that HIV-1 utilizes for its spread and the evidence pointing to cell-to-cell transmission as a mechanism for the establishment and maintenance of latent infection.