Human herpesvirus portal proteins: Structure, function, and antiviral prospects
| Autor: | Robert J. Visalli, Ellyn M. Kornfeind |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation viruses Alphaherpesvirinae Genome Antiviral Agents Bacteriophage 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Protein structure Caudovirales Virology Animals Humans Protein Interaction Domains and Motifs Herpesviridae 030102 biochemistry & molecular biology biology Herpesviridae Infections biology.organism_classification 030104 developmental biology Infectious Diseases Capsid chemistry Viral replication Structural biology Capsid Proteins Protein Multimerization DNA |
| Zdroj: | Reviews in medical virology. 28(3) |
| ISSN: | 1099-1654 |
| Popis: | Herpesviruses (Herpesvirales) and tailed bacteriophages (Caudovirales) package their dsDNA genomes through an evolutionarily conserved mechanism. Much is known about the biochemistry and structural biology of phage portal proteins and the DNA encapsidation (viral genome cleavage and packaging) process. Although not at the same level of detail, studies on HSV-1, CMV, VZV, and HHV-8 have revealed important information on the function and structure of herpesvirus portal proteins. During dsDNA phage and herpesviral genome replication, concatamers of viral dsDNA are cleaved into single length units by a virus-encoded terminase and packaged into preformed procapsids through a channel located at a single capsid vertex (portal). Oligomeric portals are formed by the interaction of identical portal protein monomers. Comparing portal protein primary aa sequences between phage and herpesviruses reveals little to no sequence similarity. In contrast, the secondary and tertiary structures of known portals are remarkable. In all cases, function is highly conserved in that portals are essential for DNA packaging and also play a role in releasing viral genomic DNA during infection. Preclinical studies have described small molecules that target the HSV-1 and VZV portals and prevent viral replication by inhibiting encapsidation. This review summarizes what is known concerning the structure and function of herpesvirus portal proteins primarily based on their conserved bacteriophage counterparts and the potential to develop novel portal-specific DNA encapsidation inhibitors. |
| Databáze: | OpenAIRE |
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