Highlighting of a LAGLIDADG and a Zing Finger Motifs Located in the pUL56 Sequence Crucial for HCMV Replication.

The human cytomegalovirus (HCMV) terminase complex is part of DNA-packaging machinery that delivers a unit-length genome into a procapsid. Sequence comparison of herpesvirus homologs allowed us to identify a potential LATLNDIERFL and zinc finger pattern in N-terminal part of pUL56. Recombinant viruses were generated with specific serine or alanine substitutions in these putative patterns.

Novel DNA polymerase mutations conferring cytomegalovirus resistance: input of BAC-recombinant phenotyping and 3D model.

Long-term exposure to antiviral therapy in immunocompromised patients favors emergence of human cytomegalovirus (HCMV) resistance mutations. Two new UL54 DNA polymerase mutations (deletion of codon 524 and N408S substitution) identified in a kidney recipient and a bone marrow recipient respectively were characterized. Marker transfer experiment through recombination into a HCMV AD169 BAC demonstrated del524 and mutation N408S confer GCV and CDV resistance.

Conserved domains and structure prediction of human cytomegalovirus UL27 protein.

Background: The human cytomegalovirus (HCMV) nuclear UL27 protein (pUL27) could be involved at the stage of nuclear egress. Maribavir is a new anti-HCMV drug that targets nuclear egress through direct inhibition of the HCMV serine-threonine kinase, UL97 protein (pUL97). Because maribavir-resistance-related mutations are observed in both proteins, pUL27 is thought to interfere with pUL97 activity; however, its mechanism of action remains unclear.

Solution and solid-state NMR of lipids.

Lipid structure and dynamics are of first importance for cellular function. Lipids such as phosphatidyl inositol (PtdIns) are essential in signaling pathways, as they are recognition sites at the membrane surface. Their headgroup or chain structure appears to be crucial for such a signaling role.

Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole D-ribonucleoside activity.

Background: 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. We aimed here to better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives.

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

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.