Mucosal infection of neonatal rhesus monkeys with cell-free SIV.

Although the mechanisms for maternal transmission are unknown, approximately half of the infants congenitally infected with the human immunodeficiency virus type 1 (HIV-1) seem to become infected late in gestation or during delivery. Previously, we have developed a rhesus monkey model for congenital infection by injecting cell-free simian immunodeficiency virus (SIV) directly into amniotic fluid. Our results suggested that fetal infection may have occurred via skin or mucous membrane exposure. Mucosal surfaces have also been implicated as a portal of virus entry by a study in which the presence of serosanguinous fluid in neonatal gastric aspirates correlated with an increased rate of HIV-1 transmission. To test whether cell-free virus could transverse intact neonatal mucosal surfaces, we administered SIVmac251 orally to four rhesus monkey neonates within 1 hr following cesarean section delivery. All four neonates developed viremia and were positive by cocultivation and PCR. Seroconversion occurred in three of the four neonates. The SIV dose given was within physiological range as shown by end-point dilution of virus stock and viremic plasma samples of juvenile rhesus monkeys. This primate model for mucosal transmission of cell-free virus features a high infection rate, thus making studies of mucosal immunity and the development of strategies to prevent intrapartum virus transmission possible.

Glycosylphosphatidylinositol-anchored CD4 supports human immunodeficiency virus type 1 replication, but not cytopathic effect, in T-cell transfectants.

Despite equivalent p24 antigen production, HSB-2 T cells expressing glycosylphosphatidylinositol (GPi)-linked CD4 were productively infected without cell death or syncytium formation, unlike HSB-2 transfectants expressing wild-type CD4 (wtCD4). HSB-2 transfectants dually expressing wtCD4 and GPi-linked CD4 formed syncytia and died. Thus, wtCD4 expression is critical for human immunodeficiency virus cytopathic effect in HSB-2 transfectants.

Intranasal monoclonal immunoglobulin A against respiratory syncytial virus protects against upper and lower respiratory tract infections in mice.

The role of secretory antibody in protection against respiratory syncytial virus (RSV) infection was examined by using monoclonal immunoglobulin A (IgA) antibody for intranasal passive immunization of mice. Eight anti-RSV IgA hybridomas were produced by fusing myeloma cells with lung lymphocytes from RSV-immunized mice. Five IgA antibodies recognized RSV strains of both the A and the B subgroups, and two of these neutralized virus in a plaque reduction assay. Monoclonal IgA antibody HNK20, which bound to F glycoprotein, was most effective, reducing plaques by 50% at a concentration of 0.1 microgram/ml for both subgroup A and subgroup B strains. HNK20 also neutralized all of eight clinical isolates of RSV tested. When delivered intranasally to mice 24 h prior to RSV challenge, HNK20 reduced virus titers in the lungs by nearly 100-fold. Maximal protection occurred at a dose of 0.5 mg/kg of body weight. Significant protection against lung infection was seen when the interval between antibody treatment and challenge was as long as 72 h. HNK20 also decreased virus titers in the nose approximately 10-fold when given 1 h, but not 24 h, before challenge. When mice were treated with HNK20 intranasally 3 days after challenge, viral titers were reduced in the lungs but not the nose. The results indicate that topical application of relatively small amounts of monoclonal IgA can protect against both upper and lower respiratory tract infections caused by RSV.