Internal Proteins of the Procapsid and Mature Capsids of Herpes Simplex Virus 1 Mapped by Bubblegram Imaging

摘要: ABSTRACT The herpes simplex virus 1 (HSV-1) capsid is a huge assembly, ∼1,250 A in diameter, and composed of thousands protein subunits with combined mass ∼200 MDa, housing 100-MDa genome. First, procapsid formed through coassembly the surface shell an inner scaffolding shell; then matures via major structural transformation, triggered by limited proteolysis proteins. Three mature capsids are found nuclei infected cells. empty, B retain shrunken shell, C capsids—which develop into infectious virions—are filled DNA ostensibly have expelled shell. possible presence other internal proteins has been moot as, cryo-electron microscopy (cryo-EM), they would be camouflaged surrounding DNA. We used bubblegram imaging to map all four capsids, aided discovery that exceptionally prone radiation-induced bubbling. confirmed this forms thick-walled shells capsid. generate two classes bubbles: one occupies positions beneath vertices icosahedral distributed throughout its interior. likely candidate viral protease. subpopulation bubbles particularly profusely may represent particles which expulsion scaffold packaging incomplete. Based on structure, we propose axial channels hexameric capsomers afford pathway expelled. IMPORTANCE In addition DNA, tailed bacteriophages their distant relatives, herpesviruses, contain These often essential for infectivity but difficult locate within virion. novel adaptation cryo-EM based detecting gas generated radiation damage was localize HSV-1, yielding insights how maturation regulated. protein, capsid, bubbling-prone. DNA-filled previously undetected underlie vertices: tentatively assigned as storage form also observed species appears substantial amounts well suggesting coupled processes.