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Many AIDS vaccine candidates under development may elicit immune responses similar to those observed in and used to screen human immunodeficiency virus type 1 (HIV-1)-infected individuals. Therefore, it is important to develop vaccine candidates that incorporate antigenic markers and allow vaccinees to be distinguished from HIV-1 infectees. To this end, we introduced a series of mutations into and in the vicinity of the major immunodominant region (MIR) of gp41 (residues 598–609), a domain recognized by almost all HIV-1 infectees, and evaluated whether HIV-1-like particles incorporating such mutant glycoproteins could be expressed in mammalian cells. Results indicated that although up to three consecutive amino acids could be replaced within MIR without significantly affecting particle formation or gp160 processing, deletions within MIR impaired envelope processing. Replacement of HIV-1 MIR by part or most of the corresponding domain from other lentiviruses markedly decreased or abolished gp160 processing. Synthetic peptides corresponding to a mutated MIR incorporating three amino acid replacements were not recognized by a panel of sera from HIV-1 infectees, suggesting that HIV-1-like particles with this type of mutation represent potential candidate vaccines that could allow vaccinees to be distinguished from HIV-1 infectees.

A liquid low-fat nutritionally adequate Metrecal diet in which alcohol contributed 37% of the total calories was given to pregnant rats and maintained during lactation. Control rats were pairfed with an isocaloric sucrose-Metrecal diet. After birth, litters were killed at different ages (days 1–30), and the results showed that growth and survival of progeny from the alcohol-treated rats were adversely affected. Likewise, the wet weights of livers from such pups were consistently less than from the pair-fed controls. The yield of hepatic plasma membrane protein per wet liver weight was constant and independent of either age or diet. Using [ 3 H]prazosin as radioligand, equilibrium binding studies were carried out to monitor changes in the structure and function of the plasma membrane in the new-born pups concomitant with the development of α 1 -adrenergic receptors. Results obtained with the alcohol-fed pups showed that the binding affinity ( K D ) was not altered throughout. However, the receptor density ( B max ) was decreased significantly. This decrease ranged from 60 to 70% in pups 6- to 15-days-old; 45% at 20 days; and 30% in pups at 25 and 30 days of age. These observations suggest that maternal ethanol ingestion affected the posrnatal development of rat liver plasma membranes. Furthermore, by using the hepatic α 1 -adrenergic receptor as a metabolic probe, we deduce that a possible impairment exists in the capacity of the alcoholic progeny to respond to the hormonal action of epinephrine. Such a defect may contribute to impaired growth and metabolism in these young animals.