DIFFERENTIAL-EFFECTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE PROTEIN GP120 ON INTERFERON-PRODUCTION BY MONONUCLEAR-CELLS FROM ADULTS AND NEONATES

While considerable progress in examining the course of human immunodef iciency virus (HIV) infection in adults has been made, a better unders tanding of the natural history of perinatal HIV infection remains to b e obtained. Dysregulation of the production and functions of various c ytokines, especially the interferons (IFNs), during HIV infections has been reported. Using an in vitro model system, we examined the effect s of the HIV type 1 envelope protein, gp120 (10, 50, and 100 ng/ml), o n gamma IFN (IFN-gamma) and IFN-alpha production by lymphocytes from n eonates and adults and also examined the potential regulatory effects of gp120 on phorbol 12-myristate acetate (PMA)- and Sendai virus-induc ed IFN-gamma and IFN-alpha production by lymphocytes. PMA at a concent ration of 50 ng/ml plus 50 ng of calcium ionophore A23187 per ml was u sed to induce IFN-gamma, while 150 hemagglutinating units of Sendai vi rus was used to induce IFN-alpha production. The antiviral activity of both IFN-alpha and IFN-gamma in leukocyte culture supernatants was as sayed on BG-9 cells by a dye uptake technique using vesicular stomatit is virus as a challenge virus. Placental cord blood leukocyte (CBL) sa mples from healthy, term infants and adult peripheral blood leukocytes (APBL) produced no IFN in response to gp120. However, CBL produced si gnificantly decreased levels of IFN-gamma compared with APBL in respon se to PMA plus ionophore. gp120 significantly suppressed both Sendai v irus-induced IFN-alpha and PMA-induced IFN-gamma production by both CB L and APBL in a dose-dependent manner. However, gpl20 induced suppress ion of IFN-alpha and IFN-gamma was significantly greater with CBL than with APBL. Treatment of CBL and APBL with gp120 did not induce any ph enotypic alteration of the CD45 RO(+) subset. Increased suppression of IFN-alpha and IFN-gamma production by gp120 in neonates may partially explain their apparent increased susceptibility to the clinical progr ession of HIV infections compared with that of adults.