TIGIT Blockade: A Multipronged Approach to Target the HIV Reservoir

During chronic human immunodeficiency virus type 1 (HIV-1) infection, upregulation of inhibitory molecules contributes to effector cell dysfunction and exhaustion. This, in combination with the ability of HIV-1 to reside dormant in cellular reservoirs and escape immune recognition, makes the pathway to HIV-1 cure particularly challenging. An idealized strategy to achieve HIV-1 cure proposes combined viral and immune activation by "shock"ing HIV-1 out of latency and into an immunologically visible state to be recognized and "kill"ed by immune effector cells. Here we outline the potential for blockade of the inhibitory immune checkpoint T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) to overcome natural killer (NK) cell and T cell inhibition associated with HIV-1 infection and invigorate antiviral effector cell responses against HIV-1 reactivated from the latent cellular reservoir.