Secretory leukocyte protease inhibitor: inhibition of human immunodeficiency virus-1 infection of monocytic THP-1 cells by a newly cloned protein Nancy R. Shine, a Susan C. Wang, b Krystyna Konopka, a, * Elizabeth A. Burks, b Nejat D€ uzg€ unes ß, a and Christian P. Whitman b, * a Department of Microbiology, School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA b Medicinal Chemistry Division, College of Pharmacy, The University of Texas, Austin, TX 78712-1074, USA Received 5 February 2002 Abstract The ability of the salivary protein, secretory leukocyte protease inhibitor (SLPI), to inhibit human immunodeficiency virus-1 (HIV-1) infection in vitro has been reported previously and has led to the suggestion that SLPI may be partially responsible for the low oral transmission rate of HIV-1. However, results contra- dictory to these findings have also been published. These discrepancies can be at- tributed to a number of factors ranging from the variability of macrophage susceptibility to HIV infection to the quality of commercially available preparations of SLPI. To resolve these differences and to study further the potential anti-HIV-1 activity of SLPI, the purified and re-folded protein, expressed from a synthetic gene, was examined using human monocytic THP-1 cells. This newly cloned SLPI reduced HIV-1 Ba-L infection in differentiated THP-1 cells, in contrast to the results observed Bioorganic Chemistry 30 (2002) 249–263 www.academicpress.com BIOORGANIC CHEMISTRY * Corresponding authors. Fax: 1-415-929-6564 (KK) and 1-512-232-2606 (CPW). E-mail addresses: kkonopka@sf.uop.edu (K. Konopka), whitman@mail.utexas.edu (C.P. Whitman). 0045-2068/02/$ - see front matter Ó 2002 Elsevier Science (USA). All rights reserved. PII:S0045-2068(02)00008-1