Major capsid reinforcement by a minor protein in herpesviruses and phage.

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Sae-Ueng U,Liu T,Catalano CE,Huffman JB,Homa FL,Evilevitch A

doi

10.1093/nar/gku634

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

9096-107

issue

14

eissn

0305-1048

issn

1362-4962

pii

gku634

journal_volume

42

pub_type

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