RESUMO
Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.
Assuntos
Sequência de Aminoácidos , Proteínas do Capsídeo , Química , Metabolismo , Microscopia Crioeletrônica , Modelos Moleculares , Dados de Sequência Molecular , Muromegalovirus , Química , Ligação Proteica , Multimerização Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de ProteínaRESUMO
Co-evolution has been shown to result in an adaptive reciprocal modification in the respective behaviors of interacting populations over time.In the case of host-parasite co-evolution,the adaptive behavior is most evident from the reciprocal change in fitness of host and parasite-manifested in terms of pathogen survival versus host resistance.Cytomegaloviruses and their hosts represent a pairing of populations that has co-evolved over hundreds of years.This review explores the pathogenetic consequences emerging from the behavioral changes caused by co-evolutionary forces on the virus and its host.