Ocular Infection

Research in Dr. Curtis Brandt's laboratory focuses on four areas of gene delivery:

1) Injection of viral gene delivery vectors into the eye triggers an inflammatory response. Researchers are trying to identify the trigger so they can block it. Currently they are looking at several pro-inflammatory cytokines such as IL-6. In addition they are making viral delivery vectors for several labs on campus.

2) Herpes simplex virus (HSV) causes blinding keratitis (inflammation of the cornea) and researchers are interested in identifying genes in the virus that contribute to severe infection. Recently, they demonstrated that multiple genes are involved and have identified a number of novel mutations in several viral proteins. New sequencing technology allows them to rapidly sequence an entire HSV genome in about a week. This allows direct comparison of virulence characteristics in animal models with the sequence of several strains to identify disease associated markers.

3) They have an active program of antiviral drug discovery and development and have worked with several companies. They have also identified novel antivirals. One was isolated from an edible mushroom that grows in Wisconsin. This novel protein appears to block several previously unknown steps in viral infection. The second group of antivirals is a series of peptides that block virus entry into cells. The peptides block HSV, Papillomavirus, HIV, and vaccinia virus. They have also shown one peptide blocks Influenza including bird flu strains. They are also using peptide based strategies to study protein function. They are currently developing the peptides as novel microbicides to block sexually transmitted viral infections. The peptides are also being used to study the poorly-understood process of viral entry.

4) One of their antiviral peptides binds to sialic acid residues on HSV-1 envelope proteins that form the fusion/entry complex. Enzymatic removal of sialic from virus particles renders them non-infectious. Researchers now know that this is because the formation of the fusion complex is triggered by desialylation. Thus sialic acid regulates fusion complex formation. They are working to identify how this occurs.