A pseudorabies virus variant (marl97-1) containing a mutation in a viral glycoprotein with a molecular weight of 50,000 (gp5O) was isolated by selecting for resistance to a neutralizing monoclonal antibody (MCA50-1) directed against gpSO. This mutant was completely resistant to neutralization with MCA50-1 in the presence or absence of complement, and was therefore defined as a mar (monoclonal-antibody-resistant) mutant. The mutation did not affect neutralization with polyvalent immune serum. The marl97-1 mutant synthesized and processed gp5O normally, but the mutation prevented the binding and immunoprecipitation of gpSO by MCA50-1. Thus, the mutation was within the structural portion of the gp5O gene affecting the epitope of the monoclonal antibody. The mutation was mapped by marker rescue with cloned pseudorabies restriction enzyme fragments to the short unique region of the pseudorabies genome between 0.813 and 0.832 map units. This is equivalent to a 2.1-kilobase-pair region.Pseudorabies virus (PRV) contains a double-stranded DNA genome with a molecular weight of ca. 90 x 106 (32).

Single and multiple doses of sCD4-PE40, a soluble recombinant fusion toxin selectively toxic to gp120-expressing cells, were evaluated in persons infected with human immunodeficiency virus type 1 (HIV-1). Seventeen of 24 patients who completed a single-dose safety trial were given either 1, 5, 10, or 15 micrograms/kg of sCD4-PE40 by intravenous bolus once a month for 2 months, then weekly for 6 weeks. The weekly maximally tolerated dose was 10 micrograms/kg. The major toxicity was a transient dose-dependent elevation in hepatic aminotransferases peaking 48 h after infusion. Anti-Pseudomonas exotoxin antibody developed in 58% of recipients, and sera from 13 of 17 showed neutralizing activity against sCD4-PE40. No consistent changes in immunologic or virologic markers were observed. Weekly infusions of < or = 10 micrograms/kg of sCD4-PE40 are generally well tolerated, but additional studies correlating optimal dosing and frequency of administration with efficacy will be needed to define the role of this novel agent in the management of HIV-1-infected patients.

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Antigenic variants of pseudorabies virus (PRV) containing mutations in a viral glycoprotein with a molecular weight of 82,000 (gIll) were isolated by selecting for resistance to a complement-dependent neutralizing monoclonal antibody (MCA82-2) directed against gIll. These mutants were completely resistant to neutralization with MCA82-2 in the presence of complement. Two mutants selected for further studies either did not express gIlI or expressed an improperly processed form of the glycoprotein. The mutations were also associated with an altered plaque morphology (syncytium formation). The gIll gene was mapped by marker rescue of a gIImutant with cloned restriction enzyme fragments to the long unique region of the PRV genome between 0.376 and 0.383 map units. This corresponds to the map location of a glycoprotein described by Robbins et al. (J. Mol. Appl. Gen. 2:485-496, 1984). Since gIll is nonessential for viral replication in cell culture and has several other characteristics in common with the herpes simplex virus glycoprotein gC, gm may represent the PRV equivalent to herpes simplex virus gC.

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