Analysis of human immunodeficiency virus matrix domain replacements

Isabel Scholz, Amelia Still, Tenzin Choesang Dhenub, Kelsey Coday, Mike Webb, Eric Barklis

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The matrix (MA) domain of the HIV-1 structural precursor Gag (PrGag) protein targets PrGag proteins to membrane assembly sites, and facilitates incorporation of envelope proteins into virions. To evaluate the specific requirements for the MA membrane-binding domain (MBD) in HIV-1 assembly and replication, we examined viruses in which MA was replaced by alternative MBDs. Results demonstrated that the pleckstrin homology domains of AKT protein kinase and phospholipase C δ1 efficiently directed the assembly and release of virus-like particles (VLPs) from cells expressing chimeric proteins. VLP assembly and release also were mediated in a phorbol ester-dependent fashion by the cysteine-rich binding domain of phosphokinase Cγ. Although alternative MBDs promoted VLP assembly and release, the viruses were not infectious. Notably, PrGag processing was reduced, while cleavage of GagPol precursors resulted in the accumulation of Pol-derived intermediates within virions. Our results indicate that the HIV-1 assembly machinery is flexible with regard to its means of membrane association, but that alternative MBDs can interfere with the elaboration of infectious virus cores.

Original languageEnglish (US)
Pages (from-to)322-335
Number of pages14
JournalVirology
Volume371
Issue number2
DOIs
StatePublished - Feb 20 2008

Fingerprint

Virion
HIV
gag Gene Products
HIV-1
Membranes
Virus Release
Virus Assembly
Protein Precursors
Type C Phospholipases
Phorbol Esters
Virus Replication
Protein Kinase C
Cysteine
Proteins
Phosphotransferases
Viruses

Keywords

  • Assembly
  • Gag
  • HIV
  • Matrix
  • Membrane
  • Retrovirus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Analysis of human immunodeficiency virus matrix domain replacements. / Scholz, Isabel; Still, Amelia; Dhenub, Tenzin Choesang; Coday, Kelsey; Webb, Mike; Barklis, Eric.

In: Virology, Vol. 371, No. 2, 20.02.2008, p. 322-335.

Research output: Contribution to journalArticle

Scholz, I, Still, A, Dhenub, TC, Coday, K, Webb, M & Barklis, E 2008, 'Analysis of human immunodeficiency virus matrix domain replacements', Virology, vol. 371, no. 2, pp. 322-335. https://doi.org/10.1016/j.virol.2007.10.010
Scholz, Isabel ; Still, Amelia ; Dhenub, Tenzin Choesang ; Coday, Kelsey ; Webb, Mike ; Barklis, Eric. / Analysis of human immunodeficiency virus matrix domain replacements. In: Virology. 2008 ; Vol. 371, No. 2. pp. 322-335.
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