PMID:25053840

Citation	Sae-Ueng, U, Liu, T, Catalano, CE, Huffman, JB, Homa, FL and Evilevitch, A (2014) Major capsid reinforcement by a minor protein in herpesviruses and phage. Nucleic Acids Res. 42:9096-107
Abstract	Herpes simplex type 1 virus (HSV-1) and bacteriophage λ capsids undergo considerable structural changes during self-assembly and DNA packaging. The initial steps of viral capsid self-assembly require weak, non-covalent interactions between the capsid subunits to ensure free energy minimization and error-free assembly. In the final stages of DNA packaging, however, the internal genome pressure dramatically increases, requiring significant capsid strength to withstand high internal genome pressures of tens of atmospheres. Our data reveal that the loosely formed capsid structure is reinforced post-assembly by the minor capsid protein UL25 in HSV-1 and gpD in bacteriophage λ. Using atomic force microscopy nano-indentation analysis, we show that the capsid becomes stiffer upon binding of UL25 and gpD due to increased structural stability. At the same time the force required to break the capsid increases by ∼70% for both herpes and phage. This demonstrates a universal and evolutionarily conserved function of the minor capsid protein: facilitating the retention of the pressurized viral genome in the capsid. Since all eight human herpesviruses have UL25 orthologs, this discovery offers new opportunities to interfere with herpes replication by disrupting the precise force balance between the encapsidated DNA and the capsid proteins crucial for viral replication.
Links	PubMed PMC4132744 Online version:10.1093/nar/gku634
Keywords	Animals; Bacteriophage lambda/metabolism; Bacteriophage lambda/physiology; Bacteriophage lambda/ultrastructure; Capsid/metabolism; Capsid/ultrastructure; Capsid Proteins/metabolism; Cercopithecus aethiops; Glycoproteins/metabolism; Herpesvirus 1, Human/metabolism; Herpesvirus 1, Human/physiology; Herpesvirus 1, Human/ultrastructure; Vero Cells; Viral Proteins/metabolism; Virus Assembly
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
LAMBD:DECO		GO:0098021: viral capsid, decoration	ECO:0000314:		C		gpD serves as a decoration protein for the capsid and leads to stronger capsid formation. Procapsids were reconstituted in vitro and expanded through 2.5 M urea treatment. Biophysical properties were then assessed through atomic force microscopy. Figure 5 and Table 2 show that addition of gpD leads to an increase in breaking force (0.78 nN from 0.45nN without gpD), and a rescue of the spring constant (0.10 N/m, compared to 0.06 N/m without gpD and the 0.11 N/m of the procapsid). Addition of gpD also reinforces the capsid's stiffness, as shown by the further increase in Young's modulus (E): 0.88 GPa with gpD, 0.57 GPa without gpD, and 0.16 GPa for the procapsid. Based on these measurements, gpD reinforces the capsid, but is not necessary to its formation.	complete CACAO 13110

References

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