
<ArticleTitle>Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by the <prot>anti-<prot>CCR5</prot> monoclonal antibody 2D7</prot>.</ArticleTitle>
<AbstractText>The second extracellular loop (ECL2) domain of <prot>CC-chemokine receptor 5</prot> (<prot>CCR5</prot>) has been proposed as a specific target site for therapeutic agents aimed at blocking <prot>CCR5</prot>-dependent entry by human immunodeficiency virus type I (HIV-1). We have adapted two <prot>CCR5</prot>-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate, 11-121, to replicate in vitro in the presence of high concentrations of a monoclonal antibody (<prot>MAb 2D7</prot>) specific for the <prot>CCR5</prot> ECL2 domain. The 75% inhibitory concentrations (IC(75)) for the two <prot>2D7</prot>-adapted isolates were approximately 100-fold higher than those for corresponding control isolates passaged without the MAb. Adapted isolates did not acquire the ability to use <prot>CXCR4</prot>, <prot>CCR3</prot>, or <prot>CCR1</prot>. Env clones derived from <prot>MAb 2D7</prot>-adapted JR-CSF showed several gp120 mutations that were not found in any of the control JR-CSF clones. The in vitro observations suggest that <prot>CCR5</prot>-using HIV-1 strains might also be able to adapt in vivo to evade an ECL2-blocking therapeutic agent.</AbstractText>
