P. Kolchinsky et al., Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication, J VIROLOGY, 73(10), 1999, pp. 8120-8126
The gp120 envelope glycoprotein of the human immunodeficiency virus type 1
(HIV-I) promotes virus entry by sequentially binding CD4 and chemokine rece
ptors on the target cell. Primary, clinical HIV-1 isolates require interact
ion with CD4 to allow gp120 to bind the CCR5 chemokine receptor efficiently
. We adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative can
ine cells expressing human CCR5. The gp120 changes responsible for the adap
tation were limited to alteration of glycosylation addition sites in the V2
loop-V1-V2 stem. The gp120 glycoproteins of the adapted viruses bound CCR5
directly, without prior interaction with CD4. Thus, a major function of CD
4 binding in the entry of primary HN-I isolates can be bypassed by changes
in I-he gp120 V1-V2 elements, which allow the envelope glycoproteins to ass
ume a conformation competent for CCR5 binding.