TY - JOUR
T1 - Relative inefficiency of soluble recombinant CD4 for inhibition of infection by monocyte-tropic HIV in monocytes and T cells
AU - Gomatos, Peter J.
AU - Stamatos, Nicholas M.
AU - Gendelman, Howard E.
AU - Fowler, Arnold
AU - Hoover, David L.
AU - Kalter, D. Chester
AU - Burke, Donald S.
AU - Tramont, Edmund C.
AU - Meltzer, Monte S.
PY - 1990/6/1
Y1 - 1990/6/1
N2 - 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 gp120, the envelope glycoprotein of HIV, and at relatively low concentrations (<1 μg/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 μg/ml sCD4: no p24 Ag or HIV-induced T cell syncytia were detected in cultures of H9 cells exposed to 1 × 104 TCID50 HTLV-IIIB in the presence of sCD4. Under identical conditions and at a 100-fold lower viral inoculum, 10 μg/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 μg/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.
AB - 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 gp120, the envelope glycoprotein of HIV, and at relatively low concentrations (<1 μg/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 μg/ml sCD4: no p24 Ag or HIV-induced T cell syncytia were detected in cultures of H9 cells exposed to 1 × 104 TCID50 HTLV-IIIB in the presence of sCD4. Under identical conditions and at a 100-fold lower viral inoculum, 10 μg/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 μg/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.
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M3 - Article
C2 - 2341717
AN - SCOPUS:0025313226
SN - 0022-1767
VL - 144
SP - 4183
EP - 4188
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -