A domain directly C-terminal to the major homology region of human immunodeficiency type 1 capsid protein plays a crucial role in directing both virus assembly and incorporation of Gag-Pol

Virology. 2006 Apr 25;348(1):84-95. doi: 10.1016/j.virol.2005.12.009. Epub 2006 Jan 25.

Abstract

We demonstrate here that a deletion of 14 amino acid residues directly C-terminal to the major homology region (MHR) of the HIV-1 capsid (CA) in Gag-Pol markedly affects the incorporation of Gag-Pol into virions. The 14-amino acid deletion also significantly impaired virus assembly. In agreement with previous reports, mutations at the very C-terminus of CA resulted in a remarkable reduction in virus production. However, HIV-1 Gag-Pol precursors containing the C-terminal CA mutation were still capable of being incorporated into virions at a level of about 50% that of the wild-type. These results suggest that the domain immediately C-terminal to the MHR is functionally involved in Gag-Gag and Gag/Gag-Pol interaction, and this supports the notion that Gag or Gag-Pol mutants blocked in assembly into virus particles can be rescued into virions provided they retain the domains that are able to interact with the Gag precursor. An HIV-1 Gag-Pol deletion mutant retaining a minimal sequence consisting of the MHR and the adjacent CA-SP1 was efficiently incorporated into virions. Analysis by immunofluorescence staining indicated that the subcellular localization patterns shown by the Gag-Pol mutants were not fully compatible with their efficiency in being incorporated into virions, suggesting that the ability of Gag-Pol mutants to be incorporated into virions largely depends on their interactions with the Gag precursor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Capsid Proteins / genetics*
  • Capsid Proteins / physiology*
  • Cell Line
  • Gene Products, gag / metabolism*
  • HIV-1 / physiology*
  • Humans
  • Microscopy, Fluorescence
  • Protein Precursors / metabolism*
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Sequence Deletion
  • Viral Proteins / analysis
  • Virus Assembly*
  • gag Gene Products, Human Immunodeficiency Virus
  • pol Gene Products, Human Immunodeficiency Virus

Substances

  • Capsid Proteins
  • Gene Products, gag
  • Protein Precursors
  • Viral Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • p55 gag precursor protein, Human immunodeficiency virus 1
  • pol Gene Products, Human Immunodeficiency Virus
  • pr160 gag-pol precursor protein, Human immunodeficiency virus 1