Keller, Paul W.;
Huang, Rick K.;
England, Matthew R.;
Waki, Kayoko;
Cheng, Naiqian;
Heymann, J. Bernard;
Craven, Rebecca C.;
Freed, Eric O.;
Steven, Alasdair C.
A Two-Pronged Structural Analysis of Retroviral Maturation Indicates that Core Formation Proceeds by a Disassembly-Reassembly Pathway Rather than a Displacive Transition
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Medientyp:
E-Artikel
Titel:
A Two-Pronged Structural Analysis of Retroviral Maturation Indicates that Core Formation Proceeds by a Disassembly-Reassembly Pathway Rather than a Displacive Transition
Beteiligte:
Keller, Paul W.;
Huang, Rick K.;
England, Matthew R.;
Waki, Kayoko;
Cheng, Naiqian;
Heymann, J. Bernard;
Craven, Rebecca C.;
Freed, Eric O.;
Steven, Alasdair C.
Erschienen:
American Society for Microbiology, 2013
Erschienen in:Journal of Virology
Sprache:
Englisch
DOI:
10.1128/jvi.01408-13
ISSN:
0022-538X;
1098-5514
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>ABSTRACT</jats:title>
<jats:p>
Retrovirus maturation involves sequential cleavages of the Gag polyprotein, initially arrayed in a spherical shell, leading to formation of capsids with polyhedral or conical morphology. Evidence suggests that capsids assemble
<jats:italic>de novo</jats:italic>
inside maturing virions from dissociated capsid (CA) protein, but the possibility persists of a displacive pathway in which the CA shell remains assembled but is remodeled. Inhibition of the final cleavage between CA and spacer peptide SP1/SP blocks the production of mature capsids. We investigated whether retention of SP might render CA assembly incompetent by testing the ability of Rous sarcoma virus (RSV) CA-SP to assemble
<jats:italic>in vitro</jats:italic>
into icosahedral capsids. Capsids were indeed assembled and were indistinguishable from those formed by CA alone, indicating that SP was disordered. We also used cryo-electron tomography to characterize HIV-1 particles produced in the presence of maturation inhibitor PF-46396 or with the cleavage-blocking CA5 mutation. Inhibitor-treated virions have a shell that resembles the CA layer of the immature Gag shell but is less complete. Some CA protein is generated but usually not enough for a mature core to assemble. We propose that inhibitors like PF-46396 bind to the Gag lattice where they deny the protease access to the CA-SP1 cleavage site and prevent the release of CA. CA5 particles, which exhibit no cleavage at the CA-SP1 site, have spheroidal shells with relatively thin walls. It appears that this lattice progresses displacively toward a mature-like state but produces neither conical cores nor infectious virions. These observations support the disassembly-reassembly pathway for core formation.
</jats:p>