Affiliation:
1. Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA
Abstract
ABSTRACT
Previous experiments identified a 12-amino-acid (aa) peptide that was sufficient to interact with the herpes simplex virus 1 (HSV-1) portal protein and was necessary to incorporate the portal into capsids. In the present study, cells were treated at various times postinfection with peptides consisting of a portion of the
Drosophila
antennapedia protein, previously shown to enter cells efficiently, fused to either wild-type HSV-1 scaffold peptide (YPYYPGEARGAP) or a control peptide that contained changes at positions 4 and 5. These 4-tyrosine and 5-proline residues are highly conserved in herpesvirus scaffold proteins and were previously shown to be critical for the portal interaction. Treatment early in infection with subtoxic levels of wild-type peptide reduced viral infectivity by over 1,000-fold, while the mutant peptide had little effect on viral yields. In cells infected for 3 h in the presence of wild-type peptide, capsids were observed to transit to the nuclear rim normally, as viewed by fluorescence microscopy. However, observation by electron microscopy in thin sections revealed an aberrant and significant increase of DNA-containing capsids compared to infected cells treated with the mutant peptide. Early treatment with peptide also prevented formation of viral DNA replication compartments. These data suggest that the antiviral peptide stabilizes capsids early in infection, causing retention of DNA within them, and that this activity correlates with peptide binding to the portal protein. The data are consistent with the hypothesis that the portal vertex is the conduit through which DNA is ejected to initiate infection.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference58 articles.
1. Metabolism of acyclovir in virus-infected and uninfected cells
2. Mechanism of action and selectivity of acyclovir;Elion GB;Am. J. Med,1982
3. Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management
4. ThompsonC WhitleyR. 2011. Neonatal herpes simplex virus infections: where are we now? Hot topics in infective immunity in children VII, p 221–230. In CurtisN FinnA PollardAJ (ed), 697 ed. Springer, New York, NY.
5. Progress in the development of new therapies for herpesvirus infections;Price NB;Curr. Opin. Virol,2011
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