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.
Bristow
C L
CL
Department of Periodontics, School of Dentistry, University of North Carolina-Chapel Hill 27599-7455, USA.
Fiscus
S A
SA
Flood
P M
PM
Arnold
R R
RR
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002462:Cell Membrane / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D015728:Receptors, HIV / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology*
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011498:Protein Precursors; D015728:Receptors, HIV; D010196:Pancreatic Elastase