Spontaneous mutations in the env gene of the human immunodeficiency virus type 1 NDK isolate are associated with a CD4-independent entry phenotype.
Human immunodeficiency virus type 1 (HIV-1) entry into target cells is a multistep process initiated by envelope protein gp120 binding to cell surface CD4. The conformational changes induced by this interaction likely favor a second-step interaction between gp120 and a coreceptor such as CXCR4 or CCR5. Here, we report a spontaneous and stable CD4-independent entry phenotype for the HIV-1 NDK isolate. This mutant strain, which emerged from a population of chronically infected CD4-positive CEM cells, can replicate in CD4-negative human cell lines. The presence of CXCR4 alone renders cells susceptible to infection by the mutant NDK, and infection can be blocked by the CXCR4 natural ligand SDF-1. Furthermore, we have correlated the CD4-independent phenotype with seven mutations in the C2 and C3 regions and the V3 loop. We propose that the mutant gp120 spontaneously acquires a conformation allowing it to interact directly with CXCR4. This virus provides us with a powerful tool to study directly gp120-CXCR4 interactions.
Dumonceaux
J
J
INSERM Unité 380 Laboratoire de Pathologie et Génétique Expérimentales, Institut Cochin de Génétique Moléculaire, Paris, France.
Nisole
S
S
Chanel
C
C
Quivet
L
L
Amara
A
A
Baleux
F
F
Briand
P
P
Hazan
U
U
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015704:CD4 Antigens / Q000502:physiology; D002460:Cell Line; D002678:Chimera / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000502:physiology
D015704:CD4 Antigens; D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4