HIV envelope gp41 x CD3

Class

Bispecific T-cell-engaging DART molecule

HIV establishes lifelong infection by inserting its genetic material into the DNA of certain immune cells, a small fraction of which persist as a 'reservoir' that current antiretroviral therapy cannot eliminate. This mechanism targets gp41, a protein fragment displayed on the surface of cells actively producing new HIV particles, and pairs recognition of gp41 with CD3, a signaling component found on all T cells. The resulting bispecific molecule, built on a dual-affinity re-targeting (DART) protein scaffold, acts as a physical bridge: one arm binds infected cells via gp41, the other arm binds and activates nearby T cells via CD3, prompting those T cells to kill the infected cell regardless of their original antigen specificity. This strategy belongs to a broader category of 'kick and kill' or reservoir-reduction approaches being explored for HIV, where latent virus is first coaxed into producing viral proteins and then eliminated by redirected immune attack. The general rationale for engaging CD3 rather than relying on a person's own antiviral T cells is that it recruits the full T-cell pool, bypassing the exhaustion and narrow specificity that often limit natural HIV-specific immunity. Beyond HIV, gp41-directed engagers illustrate a template also used against other persistent or evasive viral and tumor antigens.