Mechanism of Viral Cellular Entry

Huang, Charles

Abstract

Previously, we reported that viral fusion peptides can serve as rather specific carriers to deliver functional cargos, such as an antiviral drug or a reporter element, into cells susceptible to infection by viruses corresponding to those particular peptides. The specificity arises from the different cell surface receptors utilized by different viruses (via their fusion peptides). However, the same receptor can often be used by the fusion peptides of both human immunodeficiency virus (HIV) and its simian counterpart (SIV), even though their fusion peptides differ significantly in their amino acid sequences. Conversely the same fusion peptide can utilize one of several chemokine receptors to enter different cells. In the past year, we have concentrated on improving our experimental procedures. The type and level of expression of various receptors on different cells were estimated by flow cytometry using antibodies against the receptors. Positive controls for the immunofluorescence technique were carried out using antibodies against tubulin and clathrin. All of the results were recorded by photographs taken with both fluorescent and phase-contrast microscopy. When the amino acid sequence of the HIV fusion peptide was scrambled, the resultant peptide was unable to enter all cell lines tested, further proving that the ability of these fusion peptides to penetrate cell membranes is not due to its hydrophobicity. Furthermore, we have now obtained evidence that the HIV fusion peptide can serve as a carrier/probe for coreceptors, such as CCR4 used by T-lympocyte-tropic HIV strains and CCR5 used by macrophage-tropic HIV strains. Our observations indicate that the tropism of differing HIV strains likely resides in the differences in their gp120 surface glycoproteins. - HIV, fusion peptide, chemokine receptors, SIV, phosphatase, SET, onconase, enzyme-depletion