Affiliation:
1. Department of Experimental Medical Science, Lund University, Lund, Sweden
2. Department of Physics, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
Abstract
Most viruses undergo a maturation process from a weakly self-assembled, noninfectious particle to a stable, infectious virion. For herpesviruses, this maturation process resolves several conflicting requirements: i) assembly must be driven by weak, reversible interactions between viral particle subunits to reduce errors and minimize energy of self-assembly; ii) the viral particle must be stable enough to withstand tens of atmospheres of DNA pressure resulting from its strong confinement in the capsid. With herpes simplex virus type 1 (HSV-1) as a prototype of human herpesviruses, we demonstrate that this mechanical capsid maturation is mainly facilitated through capsid-binding auxiliary protein UL25, orthologs of which are present in all herpesviruses. Through genetic manipulation of UL25 mutants of HSV-1 combined with interrogation of capsid mechanics with atomic force microscopy nano-indentation, we suggest the mechanism of stepwise binding of distinct UL25 domains correlated with capsid maturation and DNA packaging. These findings demonstrate another paradigm of viruses as elegantly programmed nano-machines, where an intimate relationship between mechanical and genetic information is preserved in UL25 architecture.
IMPORTANCE
Minor capsid protein UL25 plays a critical role in mechanical maturation of HSV-1 capsid during virus assembly, required for stable DNA packaging. We modulate UL25-capsid interactions by genetically deleting different UL25 regions and quantify the effect on mechanical capsid stability using an atomic force microscopy (AFM) nano-indentation approach. This approach reveals how UL25 regions reinforce the herpesvirus capsid in order to stably package and retain pressurized DNA. Our data suggests a mechanism of stepwise binding of two main UL25 domains timed with DNA packaging.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference253 articles.
1. Roos WH Ivanovska IL Evilevitch A Wuite GJ. Viral capsids: mechanical
2. 482 characteristics genome packaging and delivery mechanisms. Cellular and molecular life
3. 483 sciences : CMLS. 2007;64(12):1484-97. doi: 10.1007/s00018-007-6451-1. PubMed PMID:
4. 484 17440680; PubMed Central PMCID: PMC2771126.
5. 485
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