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Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole

Gaël Champier1, Anthony Couvreux, Sébastien Hantz

  • 1Université de Limoges, Faculté de Médecine, Centre Hospitalier Universitaire Dupuytren, EA 3175, Laboratoire de Bactériologie-Virologie-Hygiène, Centre National de Référence Cytomégalovirus, Limoges, France.

Antiviral Therapy
|September 6, 2008
PubMed
Abstract

Insights

Benzimidazole derivatives inhibit human cytomegalovirus (HCMV) DNA packaging by targeting the pUL56 protein. This study reveals conserved regions in pUL56, suggesting a mechanism for DNA cleavage and viral replication inhibition.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Benzimidazole D-ribonucleosides are known inhibitors of human cytomegalovirus (HCMV) DNA packaging.
  • These compounds target the pUL56 and pUL89 subunits of the HCMV terminase complex.
  • The precise mechanism of action for benzimidazole derivatives remains incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism of HCMV DNA maturation.
  • To understand how benzimidazole derivatives inhibit viral replication.
  • To investigate the role of the pUL56 protein in DNA packaging.

Main Methods:

  • Sequence analysis of the HCMV UL56 gene and homologous genes in other herpesviruses.
  • Primary structure analysis of the corresponding amino acid sequences.
  • Comparative analysis with bacteriophage T4 gene 49 product (gp49).

Main Results:

  • Identification of 12 conserved regions within the UL56 gene across 45 HCMV strains and herpesvirus relatives.
  • Structural insights suggest the pUL56 zinc finger is spatially organized near the dimerization site.
  • This organization is proposed to facilitate DNA recognition and cleavage by the terminase complex.

Conclusions:

  • Provides a foundation for investigating the mechanism of concatemeric viral DNA cleavage.
  • Establishes a biochemical basis for the inhibition of DNA packaging by benzimidazole derivatives.
  • Offers potential targets for antiviral drug development against HCMV.

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