INHIBITION OF HIV-1 REPLICATION BY A MONOCLONAL-ANTIBODY DIRECTED TOWARD THE COMPLEMENTARITY-DETERMINING REGION 3-LIKE DOMAIN OF CD4 IN CD45 EXPRESSING AND CD45-DEFICIENT CELLS

Monoclonal antibodies directed toward the complementarity determining region (CDR)3-like loop of the aminoterminal domain of CD4 have been s hown to inhibit the replication of human immunodeficiency virus (HIV) in CD4 positive T cells. The mechanism of action of these antibodies i s not yet elucidated, although several observations suggest that they inhibit viral transcription by signal transduction through the CD4 mol ecule, potentially implicating the activation of a protein tyrosine ki nase (PTK) cascade. Since CD45 is the major protein tyrosine phosphata se associated to the plasma membrane in T cells, and has been shown to regulate the activity of several PTK, we postulated that CD45 may be necessary for the inhibitory action of the CDR3-like specific anti-CD4 antibodies. Therefore we tested the effect of one such anti-CD4 monoc lonal antibody, 13B8.2, in repressing HIV replication in CD45 positive cell lines and CD45 deficient variants. Our data show that cells resp ond to 13B8.2 postinfection treatment regardless of CD45 expression, i ndicating that neither CD45 nor PTK regulated by CD45 are implicated i n the mechanism of action of this antibody. (C) 1998 Academic Press.