Structure-function relationships of the HIV-1 envelope V3 loop tropism determinant: evidence for two distinct conformations.
OBJECTIVE
The V3 loop of the HIV-1 envelope glycoprotein gp120 is an important determinant of HIV-1-specific cell tropism. Nine different purified envelope proteins were prepared in order to examine the association between the structure of the gp120 proteins and functional properties of HIV-1 virions differing in their tropism for T-cell lines and macrophages.


RESULTS
Six monoclonal antibodies to the V3 loop reacted preferentially with T-cell line-tropic gp120 envelope proteins, and one monoclonal antibody reacted preferentially with macrophage-tropic gp120 envelope proteins. T-cell line-tropic gp120 envelope proteins were at least 10-fold more susceptible to V3 loop proteolytic cleavage by human thrombin, and 1000-fold more susceptible to V3 loop proteolytic cleavage by human mast cell tryptase than macrophage-tropic gp120 envelope proteins.


CONCLUSIONS
These findings suggest that there are two distinct conformations for the V3 loop of T-cell line-tropic and macrophage-tropic gp120 envelope proteins.
Ebenbichler
C
C
Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
Westervelt
P
P
Carrillo
A
A
Henkel
T
T
Johnson
D
D
Ratner
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D000939:Epitopes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012697:Serine Endopeptidases