EVIDENCE FOR SIMIAN IMMUNODEFICIENCY VIRUS-SPECIFIC IGM AND IGG RESPONSE IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF SERUM ENZYME-LINKED IMMUNOSORBENT ASSAY-NEGATIVE NONHUMAN-PRIMATES

In vitro polyclonal activation of peripheral blood mononuclear cells ( PBMCs) from 70% of the simian immunodeficiency virus (SIV) serum enzym e-linked, immunosorbent assay (ELISA)-negative sooty mangabeys leads t o synthesis and release of low but significant and reproducible levels of SIV-reactive antibodies, as determined by ELISA and Western blot a nalysis. The predominant isotype of SIV-reactive antibodies in the pok eweed mitogen (PWM) supernatant fluids from serum ELISA-negative manga beys is IgM, whereas the predominant isotype of SIV-reactive antibodie s in seropositive mangabeys is IgG. Depletion of CD8(+) cells led to a marked increase in the levels of SIV-reactive antibodies detected in supernatant fluids from PWM-induced cultures from the serum ELISA-nega tive mangabeys. No evidence for such SIV-reactive antibodies has been found, to date, in similar unfractionated or CD8(+) T-cell-depleted PW M-induced PBMC cultures from uninfected macaques. Supernatant fluids f rom PWM cultures of PBMCs from a select group of serum ELISA-negative mangabeys, when concentrated five times, were shown to give a Western blot profile against SIV, similar to the profile seen with plasma from seropositive infected macaques and mangabeys. Evidence is presented t o show that these serum ELISA-negative mangabeys are most likely laten tly infected with SIV. This evidence, which was obtained in samples fr om such ELISA-negative mangabeys, includes the detection of reverse tr anscriptase activity and the presence of SIV p27 in supernatant fluids of phytohemagglutinin-stimulated PBMCs in vitro. In addition, the dat a show the presence of CD8(+) T cells that regulate SIV-specific Ig sy nthesis and show the detection of gag sequences by the polymerase chai n reaction. Thus, the PWM assay described herein may provide a valuabl e additional tool for detection of lentivirus infection before or in t he absence of seroconversion.