The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes

The outcome of HIV infection in vivo and in vitro depends on the interactio n of viral and cellular genotypes, Analysis of infection of blood monocyte- derived macrophages by primary HIV strains shows that approximately one-thi rd of 32 isolates was consistently high-replicating, one-third was consiste ntly low-replicating, and one-third was dependent on the donor of the macro phages (i.e., variable). HIV isolates from patients with AIDS showed enhanc ed replication within macrophages and predominant use of CCR5 for entry, al though 13% did use CXCR4. Tissue isolates from brain and CSF showed an enha nced ability to infect 1-day-old monocytes compared with blood isolates fro m patients with AIDS. The ability of primary isolates to infect neonatal or adult monocytes maturing into macrophages or placental macrophages correla ted directly with the extent of CCR5 expression. Studies of macrophages fro m pairs of identical twins and unrelated donors showed genetic control over CCR5 expression, which was independent of the CCR5 Delta 32 genotype. Furt hermore, these studies showed a marked host-cell genetic effect on the vari able primary HIV strains. Although CCR5 was essential for the entry of most primary isolates, it was not the essential. "bottle-neck" determining prod uctivity of infection. The location of this bottleneck in the HIV replicati on cycle differs according to viral strain and host-cell donor, but it was exerted before the stage of reverse transcription in 80-90% of cases. Such host-cell genetic factors may affect viral load in vivo where macrophages a re the predominant target cells.