The host cell side of latent HIV-1 infection

The ability of HIV-1 to establish an extremely stable latent viral reservoir in the CD4 + memory T cell population prevents viral eradication with the currently available antiretroviral drugs. A viral reservoir consisting of only 10 5 latently HIV-1 infected T cells could take more than 60 years to dissipate, making natural eradication during the lifetime of a patient impossible [1]. To achieve viral eradication therapeutic intervention will be needed. The fact that latent HIV-1 infection has mostly been described in the memory T cell population, which forms part of our lifelong immunity against pathogens, seems to justify the extraordinary stability of the viral reservoir. However, while immunity is lifelong, the lifespan of individual memory T cells is limited. There is no final consent on the lifespan of memory T cells, but the higher range of estimates would suggest a half-life τ 1/2 = ~100 days for a CD4 + memory T cell, and shorter in HIV-1 patients, certainly not even in the range of the stability of the latent HIV-1 reservoir that has a calculated τ 1/2 = ~40 months [1]. To explain this discrepancy, studies have shown that latently infected T cells can undergo homeostatic proliferation in the absence of HIV-1 reactivation [2] as to maintain stability of the latent reservoir. HIV-1 integration into genes that promote clonal expansion of latently HIV-infected cells and slow the decay of the viral reservoir has also been described [3]. Viral reservoirs have been described in central memory T cells (T CM) and in effector memory T cells (T EM), and a more recent study described initial progressive reservoir contraction until a steady state in an extremely stable reservoir around a core of less-differentiated, stem cell-like memory CD4+ T cells (T SCM) was achieved [4]. However, no matter the exact nature of host cells of the latent HIV-1 reservoir, under the assumption that latent HIV-1 infection events are established in functional memory T cells, we should observe continuous and complete contraction of the reservoir as these T cells encounter their cognate antigen over time, as a cognate antigen induced recall response should then trigger HIV-1 reactivation. If latent HIV-1 infection were associated with functional memory T cells, to explain the reservoir stability, latent HIV-1 infection events would have to be exclusively established in memory T cells that recognize extremely rare antigens, or would have to be established in T cells that recognize …