Michael Swanson
e-mail address: micswans@umich.edu

Mentor: David Markovitz, MD

Research Description

After over 25 years of HIV research, an effective vaccine to prevent HIV/AIDS remains elusive. Until a vaccine is found, new agents for prevention and for anti-viral therapy will be needed. Lectins, carbohydrate binding proteins of non-immune origin, make up a group of potential anti-viral agents. The HIV-1 envelope protein contains numerous glycosylation sites, including those composed of high-mannose structures. Mannose specific lectins have been shown to inhibit HIV-1 infection in vitro by binding to the glycosylated envelope of the virus. BanLec is a mannose/glucose specific lectin isolated from bananas and thus we hypothesized that BanLec inhibits HIV-1 infection. This lectin has prevented infection of an HIV-1 indicator cell line, primary monocyte-derived macrophages, and peripheral blood lymphocytes by various strains of HIV-1. To determine the potential for BanLec to be utilized as a microbicide, we will compare its inhibitory potency to that of other lectins considered as possible microbicide candidates. In addition, we will further investigate the mitogenicity and toxicity profiles of BanLec. A recombinant version of BanLec has been made to ease production of the lectin and to allow for site-directed mutagenesis. The ability of recombinant BanLec to inhibit HIV-1 replication will be compared to that of naturally derived BanLec, and site-directed mutagenesis will be used to improve its antiviral and toxicity properties. Ultimately, the goal of this work is to develop a BanLec based topical microbicide that can inhibit HIV-1 transmission.

Publications

Banerjee, A.L; Tobwala, S.; Haldar, M.K.; Swanson, M.; Roy, B.C.; Mallik, S.; Srivastava, D.K. Inhibition of matrix metalloproteinase-9 by “multi-prong” surface binding groups. Chemical Communications, 2005, 2549 – 2551.

Roy, B. C.; Banerjee, A. L.; Swanson, M.; Jia, X. G.; Haldar, M. K.; Mallik, S.; Srivastava, D. K., Two-Prong Inhibitors for Human Carbonic Anhydrase II. J. Am. Chem. Soc., 2004, 126(41), 13206-13207.

Banerjee, A. L.; Swanson, M.; Roy, B. C.; Jia, X.; Haldar, M. K.; Mallik, S.; Srivastava, D. K., Protein Surface-Assisted Enhancement in the Binding Affinity of an Inhibitor for Recombinant Human Carbonic Anhydrase-II. J. Am. Chem. Soc, 2004; 126(35) 10875-10883

Banerjee AL, Swanson M, Mallik S, Srivastava DK, Purification of recombinant human carbonic anhydrase-II by metal affinity chromatography without incorporating histidine tags. Protein Expr Purif. 2004 Oct; 37(2),450-454.

Abstracts

Swanson, M., Winter, H.C., Goldstein, I.J., Markovitz, D.M. (2008). Inhibition of HIV-1 by BanLec. Poster presentation at the 25 Years of HIV at the Pasteur Institute meeting at Paris, France.

Awards

Rackham Predoctoral Travel Grant, 2010