3 research outputs found
Structure and uncoating of immature adenovirus
Maturation via proteolytical processing is a common trait in the viral world, and is
often accompanied by large conformational changes and rearrangements in the capsid.
The adenovirus protease has been shown to play a dual role in the viral infectious
cycle: (a) in maturation, as viral assembly starts with precursors to several of the
structural proteins, but ends with proteolytically processed versions in the mature
virion; and (b) in entry, because protease-impaired viruses have difficulties in
endosome escape and uncoating. Indeed, viruses that have not undergone proteolytical
processing are not infectious. We present the 3D structure of immature adenovirus
particles, as represented by the thermosensitive mutant Ad2 ts1 grown under nonpermissive
conditions, and compare it with the mature capsid. Our 3DEM maps at
subnanometer resolution indicate that adenovirus maturation does not involve large
scale conformational changes in the capsid. Difference maps reveal the location of
unprocessed peptides pIIIa and pVI and help to define their role in capsid assembly
and maturation. An intriguing difference appears in the core, indicating a more
compact organization and increased stability of the immature cores. We have further
investigated these properties by in vitro disassembly assays. Fluorescence and
electron microscopy experiments reveal differences in the stability and uncoating of
immature viruses, both at the capsid and core levels, as well as disassembly
intermediates not previously imaged.This work was supported by grants from the Ministerio de Ciencia e Innovación of Spain (BFU2007-60228 to C.S.M. and BIO2007-67150-C03-03 to R.M.), the Comunidad Autónoma de Madrid and Consejo Superior de Investigaciones CientÃficas (CCG08-CSIC/SAL-3442 to C.S.M.) and the National Institutes of Health (5R01CA111569 to D.T.C., R0141599 to W.F.M. and GM037705 to S.J.F.). R.M.-C. is a recipient of a PFIS fellowship from the Instituto de Salud Carlos III of Spain. A.J.P.-B. holds a CSIC JAE-Doc postdoctoral position, partially funded by the European Social FundPeer reviewe
Structure and uncoating of immature adenovirus
Maturation via proteolytical processing is a common trait in the viral world, and is
often accompanied by large conformational changes and rearrangements in the capsid.
The adenovirus protease has been shown to play a dual role in the viral infectious
cycle: (a) in maturation, as viral assembly starts with precursors to several of the
structural proteins, but ends with proteolytically processed versions in the mature
virion; and (b) in entry, because protease-impaired viruses have difficulties in
endosome escape and uncoating. Indeed, viruses that have not undergone proteolytical
processing are not infectious. We present the 3D structure of immature adenovirus
particles, as represented by the thermosensitive mutant Ad2 ts1 grown under nonpermissive
conditions, and compare it with the mature capsid. Our 3DEM maps at
subnanometer resolution indicate that adenovirus maturation does not involve large
scale conformational changes in the capsid. Difference maps reveal the location of
unprocessed peptides pIIIa and pVI and help to define their role in capsid assembly
and maturation. An intriguing difference appears in the core, indicating a more
compact organization and increased stability of the immature cores. We have further
investigated these properties by in vitro disassembly assays. Fluorescence and
electron microscopy experiments reveal differences in the stability and uncoating of
immature viruses, both at the capsid and core levels, as well as disassembly
intermediates not previously imaged.This work was supported by grants from the Ministerio de Ciencia e Innovación of Spain (BFU2007-60228 to C.S.M. and BIO2007-67150-C03-03 to R.M.), the Comunidad Autónoma de Madrid and Consejo Superior de Investigaciones CientÃficas (CCG08-CSIC/SAL-3442 to C.S.M.) and the National Institutes of Health (5R01CA111569 to D.T.C., R0141599 to W.F.M. and GM037705 to S.J.F.). R.M.-C. is a recipient of a PFIS fellowship from the Instituto de Salud Carlos III of Spain. A.J.P.-B. holds a CSIC JAE-Doc postdoctoral position, partially funded by the European Social FundPeer reviewe