ITIH4 and HIV-1 infection: During natural HIV-1 infection, Env is presented to the human humoral immune system in various forms, but importantly as functional Env trimers on the surface of virions and infected cells, together with the disassembled or conformationally open Env trimers, shed monomeric gp120 and residual gp41 stumps and aggregated gp160 from the infected cells [28, 29].