Inhibition of Serum-Enhanced HIV-1 Infection of U937 Monocytoid Cells by Recombinant Soluble CD4 and Anti-CD4 Monoclonal Antibody

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Abstract
Mononuclear phagocytes can be infected with the human immunodeficiency virus type 1 (HIV-1). Although these cells express CD4 antigen, which is the recognized cellular receptor for HIV, additional cell surface proteins such as the Fc receptor, might serve as receptors for infection. In order to study this possibility we used the U937 monocytic cell line as a target for HIV infection. Flow cytometry of U937 showed that 97% of cells expressed CD4, 33% expressed the high affinity 72 kD Fc receptor (FcRI), and 74% expressed the low-affinity 40 kD Fc receptor (FcRII). Virus neutralization tests were performed by preincubating heat-inactivated human anti-HIV sera with HIV-1, IIIB strain, and then challenging U937. After 13 days in culture, productive HIV-1 infection was monitored by reverse transciptase activity. High concentrations of certain sera (10-1-10-3 dilutions) neutralized HIV-1, but at subneutralizing concentrations (10-4-10-6 dilutions), five of these sera enhanced viral infection approximately two- to threefold. This enhancement of HIV-1 infection was totally blocked by 1 μg/ml recombinant soluble CD4 (rCD4) or by 0.5 μg/ml anti-CD4 Leu3a monoclonal antibody. These results suggest that serum enhancement of HIV-1 infection, thought to be due to binding to the monocyte Fc receptor, requires HIV-1 binding to CD4, since rCD4 or Leu3a blocked this phenomenon.