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Comment
. 2002 Feb 19;99(4):1749-51.
doi: 10.1073/pnas.042708299.

HIV's response to a CCR5 inhibitor: I'd rather tighten than switch!

Joshua M Farber  1 , Edward A Berger
Affiliations
Comment

HIV's response to a CCR5 inhibitor: I'd rather tighten than switch!

Joshua M Farber et al. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Figure 1
Figure 1
Sequential receptor interactions involved in HIV-1 entry into T cells. In the report by Trkola et al. (3), the initial virus population used CCR5 but not CXCR4.
Figure 2
Figure 2
Potential viral escape mechanisms from CCR5-targeted inhibitor AD101. The normal gp120/CCR5 interaction (A) is blocked when AD101 (*) binds specifically to CCR5, thereby preventing membrane fusion and virus entry (B). Several mutational variations in gp120 can be envisioned that would lead to viral escape from AD101, including: change (or expansion) of coreceptor usage to enable CXCR4 usage (C); increased affinity of gp120 for CCR5, thereby enabling more efficient competition with AD101 for binding to CCR5 (D); acquisition of the ability of gp120 to function with CCR5 bound to AD101. In the study by Trkola et al., no evidence for escape mechanism C was detected. The authors propose a sequential resistance pathway, involving first adaption to more efficient use of CCR5 (D) followed by selection for variants that can use the drug-bound form of CCR5 (E).
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References

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