Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus type 1 entry?

Despite being able to use the Bonzo coreceptor as efficiently as CCR5 in tr ansfected cells, pediatric human immunodeficiency virus type 1 isolate P6 w as unable to replicate in peripheral blood mononuclear cells (PBMC) lacking the CCR5 receptor. Furthermore, its replication in wild-type PBMC was comp letely inhibited by inhibitors of CCR5-mediated entry. Similarly, maternal isolate M6 could use CCR5, CXCR4, Bonzo, and other coreceptors in transfect ed cells but was completely sensitive to inhibitors of CCR5- and CXCR4-medi ated entry when grown in PBMC. The ability of these viruses to use corecept ors in addition to CCR5- and CXCR4 in vitro was, therefore, irrelevant to t heir drug sensitivity in primary cells. We argue that CCR5 and CXCR4 should remain the primary targets for antiviral drug development, pending strong evidence to the contrary.