Impact of natural sequence variation in the V2 region of the envelope protein of human immunodeficiency virus type 1 on syncytium induction: a mutational analysis.
Several studies have demonstrated a functional role for the V1-V2 region of the human immunodeficiency virus type 1 (HIV-1) envelope surface glycoprotein gp120 in the membrane fusion processes underlying viral entry and syncytium induction. In a study with chimeric primary envelope genes, we have previously demonstrated that the exchange of V2 regions was sufficient to transfer syncytium-inducing capacity to a non-syncytium-inducing envelope protein. The exchanged V2 regions, comprising a number of variable amino acids, conferred changes to both the predicted secondary structure and to the net positive charge of the V2 loops. In a syncytium-forming assay based on transient envelope protein expression in CD4+ SupT1 cells, we have extended this observation by mutating the variable positions of the V2 region to determine the relative contribution of individual amino acids to syncytium formation. It can be shown that simultaneous mutation of multiple amino acids is needed to interfere with the V2 region-determined syncytium-inducing phenotype. Single amino acid changes either influencing charge of predicted secondary structure of the V2 loop proved to be insufficient to abolish V2 region-controlled syncytium formation. This robust V2 organization may allow the virus to accumulate mutations, while retaining its biological phenotype.
Andeweg
A C
AC
Laboratory of Immunobiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Boers
P H
PH
Osterhaus
A D
AD
Bosch
M L
ML
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000502:physiology; D001483:Base Sequence; D002478:Cells, Cultured; D004563:Electrochemistry; D015752:Genes, env / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000821:virology; D014162:Transfection
D000596:Amino Acids; D015699:HIV Envelope Protein gp120; D011993:Recombinant Fusion Proteins