Alteration and analyses of viral entry with library-derived peptides

The use of peptide libraries has revolutionized the ability to mutate and alter various properties of proteins. Initial studies employing peptide libraries utilized bacteriophage as a display platform (Cwirla et al., 1990; Devlin et al., 1990; Scott and Smith, 1990) or synthetic peptides on beads (Geysen et al., 1984; Lam et al., 1991). The initial applications screened simply for peptides binding to target molecules (streptavidin) (Devlin et al., 1990; Lam et al., 1991), or for peptide epitopes that bound to antibodies (Cwirla et al., 1990; Geysen et al., 1984; Scott and Smith, 1990). Since then, vast amounts of literature have been published employing peptide display libraries to alter and analyze various characteristics of proteins. In this chapter, we discuss the use of peptide libraries to examine and alter the interactions of mammalian viruses with cellular receptors. Investigations using antibodies derived from library screens to study immunological aspects of viruses and/or alter virus-cell interactions will not be discussed. Screening peptide libraries is a useful method for targeting retroviral, adenoviral, and adeno-associated viral gene therapy vectors to specific cells. In the case of adenovirus (Ad) and adeno-associated virus (AAV), peptides have been obtained from phage display libraries and attached to the surface of the virus, resulting in new targeting properties. Libraries of AAV and retroviral peptide display particles have also been employed in the development of gene therapy vectors. © 2005 Elsevier Inc. All rights reserved.