title: Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells.
abstract: Macrophages are major viral reservoirs in the brain, lungs, and lymph nodes of HIV-infected patients. But not all HIV isolates infect macrophages. The molecular basis for this restrictive target cell tropism and the mechanisms by which HIV infects macrophages are not well understood: virus uptake by CD4-dependent and -independent pathways have both been proposed. Soluble rCD4 (sCD4) binds with high affinity to gp 120, the envelope glycoprotein of HIV, and at relatively low concentrations (less than 1 microgram/ml) completely inhibits infection of many HIV strains in T cells or T cell lines. HTLV-IIIB infection of the H9 T cell line was completely inhibited by prior treatment of virus with 10 micrograms/ml sCD4: no p24 Ag or HIV-induced T cell syncytia were detected in cultures of H9 cells exposed to 1 x 10(4) TCID50 HTLV-IIIB in the presence of sCD4. Under identical conditions and at a 100-fold lower viral inoculum, 10 micrograms/ml sCD4 had little or no effect on infection of monocytes by any of six different HIV isolates by three different criteria: p24 Ag release, virus-induced cytopathic effects, and the frequency of infected cells that express HIV-specific mRNA. At 10- to 100-fold higher concentrations of sCD4, however, infection was completely inhibited. Monoclonal anti-CD4 also prevented infection of these same viral isolates in monocytes. The relative inefficiency of sCD4 for inhibition of HIV infection in monocytes was a property of the virion, not the target cell: HIV isolates that infect both monocytes and T cells required similarly high levels of sCD4 (100 to 200 micrograms/ml) for inhibition of infection. These data suggest that the gp120 of progeny HIV derived from macrophages interacts with sCD4 differently than that of virions derived from T cells. For both variants of HIV, however, the predominant mechanism of virus entry for infection is CD4-dependent.
authors.affiliation: Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gomatos
authors.forename: N M
authors.initials: NM
authors.lastname: Stamatos
authors.forename: H E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: A
authors.initials: A
authors.lastname: Fowler
authors.forename: D L
authors.initials: DL
authors.lastname: Hoover
authors.forename: D C
authors.initials: DC
authors.lastname: Kalter
authors.forename: D S
authors.initials: DS
authors.lastname: Burke
authors.forename: E C
authors.initials: EC
authors.lastname: Tramont
authors.forename: M S
authors.initials: MS
authors.lastname: Meltzer
mesh_terms: D015704:CD4 Antigens / Q000008:administration & dosage / Q000627:therapeutic use*; D003588:Cytopathogenic Effect, Viral; D015658:HIV Infections / Q000382:microbiology / Q000517:prevention & control*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009000:Monocytes / Q000382:microbiology*; D011994:Recombinant Proteins; D012995:Solubility; D013601:T-Lymphocytes / Q000382:microbiology*
chemical_list: D015704:CD4 Antigens; D011994:Recombinant Proteins