Document Detail

Proteolytic processing of the p2/nucleocapsid cleavage site is critical for human immunodeficiency virus type 1 RNA dimer maturation.
MedLine Citation:
PMID:  11533179     Owner:  NLM     Status:  MEDLINE    
Differences in virion RNA dimer stability between mature and protease-defective (immature) forms of human immunodeficiency virus type 1 (HIV-1) suggest that maturation of the viral RNA dimer is regulated by the proteolytic processing of the HIV-1 Gag and Gag-Pol precursor proteins. However, the proteolytic processing of these proteins occurs in several steps denoted primary, secondary, and tertiary cleavage events and, to date, the processing step associated with formation of stable HIV-1 RNA dimers has not been identified. We show here that a mutation in the primary cleavage site (p2/nucleocapsid [NC]) hinders formation of stable virion RNA dimers, while dimer stability is unaffected by mutations in the secondary (matrix/capsid [CA], p1/p6) or a tertiary cleavage site (CA/p2). By introducing mutations in a shared cleavage site of either Gag or Gag-Pol, we also show that the cleavage of the p2/NC site in Gag is more important for dimer formation and stability than p2/NC cleavage in Gag-Pol. Electron microscopy analysis of viral particles shows that mutations in the primary cleavage site in Gag but not in Gag-Pol inhibit viral particle maturation. We conclude that virion RNA dimer maturation is dependent on proteolytic processing of the primary cleavage site and is associated with virion core formation.
M Shehu-Xhilaga; H G Kraeusslich; S Pettit; R Swanstrom; J Y Lee; J A Marshall; S M Crowe; J Mak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  75     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-09-04     Completed Date:  2001-10-11     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9156-64     Citation Subset:  IM    
AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.
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MeSH Terms
Gene Products, gag / chemistry,  physiology*
HIV Infections / virology*
HIV-1 / physiology*
Nucleic Acid Conformation
RNA, Viral / chemistry,  physiology
Virus Replication
Grant Support
Reg. No./Substance:
0/Gene Products, gag; 0/RNA, Viral

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