title: The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes.
abstract: The outcome of HIV infection in vivo and in vitro depends on the interaction of viral and cellular genotypes. Analysis of infection of blood monocyte-derived macrophages by primary HIV strains shows that approximately one-third of 32 isolates was consistently high-replicating, one-third was consistently low-replicating, and one-third was dependent on the donor of the macrophages (i.e., variable). HIV isolates from patients with AIDS showed enhanced replication within macrophages and predominant use of CCR5 for entry, although 13% did use CXCR4. Tissue isolates from brain and CSF showed an enhanced ability to infect 1-day-old monocytes compared with blood isolates from patients with AIDS. The ability of primary isolates to infect neonatal or adult monocytes maturing into macrophages or placental macrophages correlated directly with the extent of CCR5 expression. Studies of macrophages from pairs of identical twins and unrelated donors showed genetic control over CCR5 expression, which was independent of the CCR5delta32 genotype. Furthermore, these studies showed a marked host-cell genetic effect on the variable primary HIV strains. Although CCR5 was essential for the entry of most primary isolates, it was not the essential "bottleneck" determining productivity of infection. The location of this bottleneck in the HIV replication 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 are the predominant target cells.
authors.affiliation: Centre for Virus Research, The Westmead Millennium Institute, University of Sydney, Australia. tony_cunningham@wmi.usyd.edu.au
authors.forename: A L
authors.initials: AL
authors.lastname: Cunningham
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Juarez
authors.forename: G
authors.initials: G
authors.lastname: Lynch
authors.forename: M
authors.initials: M
authors.lastname: Alali
authors.forename: H
authors.initials: H
authors.lastname: Naif
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000235:genetics / Q000821:virology; D005838:Genotype; D006678:HIV / Q000235:genetics* / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000502:physiology / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication