Inhibition of HIV-1 by modification of a host membrane protease |
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Authors: | Bristow, Cindy L. Fiscus, Susan A. Flood, Patrick M. Arnold, Roland R. |
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Affiliation: | 1 Dental Research Center, 1Department of Periodontics, School of Dentistry University of North Carolina—Chapel Hill Chapel Hill, NC 27599-7455, USA 2 Dental Research Center, 2core Retrovirology Laboratory, University of North Carolina—Chapel Hill Chapel Hill, NC 27599-7455, USA |
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Abstract: | While it is clear that CD4 Is the receptor for the gp120 envelopeprotein of HIV-1, substantial evidence suggests that other hostcell proteins are required for successful membrane fusion. Studieswere initiated to examine the potential for a protein receptorwhich has an elastase-like character to participate in fusionof HIV-1 with permissive host cells. A synthetic elastase inhibitorwas shown to significantly reduce HIV-1 infectivity when presentduring, but not after, the initial contact between virus andcells. A human T cell elastase-like membrane component was purifiedand shown to be lipid-associated. By competitive Inhibition,the purified protein was shown to bind gp160 within the HIV-1fusion domain. The binding parameters of whole T cell membraneextract, with a hydrophobic pentapeptide representative of thefusion domain, suggested an elastase-like protein is the single,secondary T cell receptor for HIV-1 (K = 1x103 M–1). Thepentapeptide interacted with porcine and human (epithelial andpolymorphonuclear leukocyte), but not murine, elastase isoforms,suggesting its participation In the permissiveness of host cellsto infection. |
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Keywords: | /math/alpha.gif" ALT=" {alpha}" BORDER=" 0" >1-antitrypsin /math/alpha.gif" ALT=" {alpha}" BORDER=" 0" >1-protease inhibitor CD4 elastase gp 120 gp41 HIV-1 T cell |
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