Naturally occurring amino acid substitutions in the HIV-2 ROD envelope glycoprotein regulate its ability to augment viral particle release.
The envelope glycoprotein of HIV-2 ROD10 has the intriguing ability to enhance the rate of viral particle release from infected cells. However, not all HIV-2 envelope glycoproteins are active in this regard. Indeed, we have previously noted that, despite a high degree of identity with that of ROD10, the envelope protein of the ROD14 isolate was unable to enhance virus production. In this study, site-directed mutagenesis was employed to reveal that a single naturally occurring alanine-to-threonine substitution at position 598, located in the extracellular part of the TM subunit, fully accounted for the lack of activity of the ROD14 Env in HeLa and 12D7 cells. A second mutation at position 422, substituting a lysine residue in ROD10 for an arginine in ROD14, was additionally required for efficient virus release from infected H9 cells, suggesting cell-type-specific requirements for this activity. Interestingly, the ROD14 Env protein exhibited a trans-dominant negative effect on particle release by ROD10 Env, suggesting that the viral release activity of the HIV-2 ROD envelope protein may be regulated by its ability to assemble into functional oligomeric structures.
Viral Biochemistry Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA. sbour@niaid.nih.gov
Stephan
S
Bour
Hirofumi
H
Akari
Eri
E
Miyagi
Klaus
K
Strebel
D019943:Amino Acid Substitution; D003001:Cloning, Molecular; D015686:Gene Products, env / Q000235:genetics* / Q000502:physiology; D015498:HIV-2 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014779:Virus Replication / Q000502:physiology*
D015686:Gene Products, env; D011994:Recombinant Proteins