HIV Type 1 Molecular Clones Able to Use the Bonzo/STRL-33 Coreceptor for Virus Entry

Abstract

We describe the cloning of env genes from the mother-infant HIV-1 isolate pair P6-v3 and M6-v3. These viruses are unusual in that they can use the coreceptor Bonzo/STRL33 as well as CCR5 and, in the case of M6, CXCR4, to enter transfected cell lines in vitro. The phenotype of the parental isolates is generally reflected by the properties of the cloned env genes, when these are used in an Env-complementation assay of virus entry. Chimeric viruses were also made that contain the env genes of P6-v3 and M6-v3 inserted into the background of the infectious molecular clone, HIV-1 NL4-3. Some of the chimeric viruses derived from HIV1 P6-v3 were able to use Bonzo for entry into transfected cell lines, albeit to a lesser extent than they could use CCR5. There are some indications that one of these chimeric viruses, P6-v3-22-1, can use a coreceptor other than CCR5, perhaps Bonzo, to enter mitogen-stimulated PBMC, although only weakly. However, formal proof that this virus can use Bonzo in primary cells has not been obtained. The P6-v3-22-1 chimeric virus was unable to infect CD4-negative, placental cell lines, in the presence or absence of soluble CD4. Env sequence analysis revealed several differences among viruses with different tropisms, most notably a four amino acid deletion in the central region of the V3 loop that distinguishes the R5 virus P6-v3-25-4 from the R5, Bonzo virus P6-v3-22-1.