Human immunodeficiency virus type 1 escape from cyclotriazadisulfonamide-induced CD4-targeted entry inhibition is associated with increased neutralizing antibody susceptibility.
Continuous specific downmodulation of CD4 receptor expression in T lymphocytes by the small molecule cyclotriazadisulfonamide (CADA) selected for the CADA-resistant human immunodeficiency virus type 1 (HIV-1) NL4.3 virus containing unique mutations in the C4 and V5 regions of gp120, likely stabilizing the CD4-binding conformation. The amino acid changes in Env were associated with decreased susceptibility to anti-CD4 monoclonal antibody treatment of the cells and with higher susceptibility of the virus to soluble CD4. In addition, the acquired ability of a CADA-resistant virus to infect cells with low CD4 expression was associated with an increased susceptibility of the virus to neutralizing antibodies from sera of several HIV-1-infected patients.
Vermeire
Kurt
K
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. kurt.vermeire@rega.kuleuven.be
Van Laethem
Kristel
K
Janssens
Wouter
W
Bell
Thomas W
TW
Schols
Dominique
D
D000914:Antibodies, Viral / Q000494:pharmacology*; D015704:CD4 Antigens / Q000187:drug effects* / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009154:Mutation; D015728:Receptors, HIV / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
D000914:Antibodies, Viral; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV; D011994:Recombinant Proteins; D013449:Sulfonamides; C076613:recombinant soluble CD4