A useful viral reagent should generally encode a primary HIV-1 Env with a closed conformation and tier 2 neutralization resistance, be transmissible via parenteral and mucosal routes, infect appropriate target cells, exhibit reliable viral replication kinetics, lead to HIV-like pathogenesis and immunobiology, display relevant bnAb epitopes, and engage innate and adaptive immune responses akin to HIV-1 infection. The gene discussed is ERVW-1; the disease is HIV-1 infection.