Analysis of human immunodeficiency virus type 1 Gag dimerization-induced assembly

Ayna Alfadhli, Tenzin Choesang Dhenub, Amelia Still, Eric Barklis

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.

Original languageEnglish (US)
Pages (from-to)14498-14506
Number of pages9
JournalJournal of Virology
Volume79
Issue number23
DOIs
StatePublished - Dec 2005

Fingerprint

gag Gene Products
Nucleocapsid
dimerization
Dimerization
Human immunodeficiency virus 1
Human Immunodeficiency Virus gag Gene Products
HIV-1
Capsid
nucleocapsid
capsid
Cysteine
cysteine
proteins
Virus Assembly
Retroviridae
RNA
Viral RNA
nucleocapsid proteins
virus-like particles
Virion

ASJC Scopus subject areas

  • Immunology

Cite this

Analysis of human immunodeficiency virus type 1 Gag dimerization-induced assembly. / Alfadhli, Ayna; Dhenub, Tenzin Choesang; Still, Amelia; Barklis, Eric.

In: Journal of Virology, Vol. 79, No. 23, 12.2005, p. 14498-14506.

Research output: Contribution to journalArticle

Alfadhli, Ayna ; Dhenub, Tenzin Choesang ; Still, Amelia ; Barklis, Eric. / Analysis of human immunodeficiency virus type 1 Gag dimerization-induced assembly. In: Journal of Virology. 2005 ; Vol. 79, No. 23. pp. 14498-14506.
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