Inhibition of HIV-1 by modification of a host membrane protease.

While it is clear that CD4 is the receptor for the gp120 envelope protein of HIV-1, substantial evidence suggests that other host cell proteins are required for successful membrane fusion. Studies were initiated to examine the potential for a protein receptor which has an elastase-like character to participate in fusion of HIV-1 with permissive host cells. A synthetic elastase inhibitor was shown to significantly reduce HIV-1 infectivity when present during, but not after, the initial contact between virus and cells. A human T cell elastase-like membrane component was purified and shown to be lipid-associated. By competitive inhibition, the purified protein was shown to bind gp160 within the HIV-1 fusion domain. The binding parameters of whole T cell membrane extract, with a hydrophobic pentapeptide representative of the fusion domain, suggested an elastase-like protein is the single, secondary T cell receptor for HIV-1 (K = 1 x 10(3) M-1). The pentapeptide interacted with porcine and human (epithelial and polymorphonuclear leukocyte), but not murine, elastase isoforms, suggesting its participation in the permissiveness of host cells to infection.