New functional domains of human cytomegalovirus pUL89 predicted by sequence analysis and three-dimensional modelling of the catalytic site DEXDc

Gaël Champier , Sébastien Hantz (1, 2) , Anthony Couvreux , Stéphanie Stuppfler , Marie-Christine Mazeron (3) , Serge Bouaziz , François Denis (1, 2) , Sophie Alain (1, 2)

1 EA3175 - Biologie moléculaire et cellulaire des microorganismes
2 UNILIM - Université de Limoges
3 Hôpital Lariboisière

INTRODUCTION: Benzimidazole D-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89, the large and small subunits of the HCMV terminase respectively, their mechanism of action is not yet fully understood. METHODS AND RESULTS: To better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives, we studied the HCMV pUL89 protein by a genetic approach combined with primary structure analysis. The pUL89 sequence analysis of 25 HCMV strains and counterparts among herpesviruses allowed identification of 12 conserved regions. We also built a three-dimensional model of the pUL89 ATPasic catalytic site, including ATPase motor motifs 1, II and III, that may facilitate the development of future antiviral drugs active against HCMV. Finally, we identified several putative functional domains in pUL89, such as pUL89 zinc finger (pUL89-ZF), DNA cutting sites and portal binding sites, that are probably involved in CMV DNA cleavage and packaging.

Domaines: Bactériologie; Virologie; Maladies infectieuses

Gaël Champier, Sébastien Hantz, Anthony Couvreux, Stéphanie Stuppfler, Marie-Christine Mazeron, et al.. New functional domains of human cytomegalovirus pUL89 predicted by sequence analysis and three-dimensional modelling of the catalytic site DEXDc. Antiviral Therapy, 2007, 12 (2), pp.217-232. ⟨hal-00406797⟩