Therapeutic Strategy for the Prevention of Pseudorabies Virus Infection in C57BL/6 Mice by 308 scFv with Intrinsic Nuclease Activity

Abstract

308 single chain variable fragment (scFv) is a recombinant monoclonal antibody with nuclease activity that was originally isolated from autoimmune-prone MRL mice. In a previous study, we analyzed the nuclease activity of 308 scFv and determined that a He La cell line expressing 308 scFv conferred resistance to herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV). In this study, we demonstrate that 308 scFv could be delivered to target tissues and cells where it exerted a therapeutic effect against PRV. PRV was inoculated via intramuscular injection, and 308 scFv was injected intraperitoneally. The observed therapeutic effect of 308 scFv against PRV was also supported by results from quantitative reverse transcription polymerase chain reaction, southern hybridization, and immunohistochemical assays. Intraperitoneal injection of 5 and 10 jig 308 scFv resulted in no detectable toxicity The survival rate in C57BU6 mice was 9% after intramuscular injection of 10 LD50 PRV. In contrast, the 308 scFv-injected C57BU6 mice showed survival rates of 57% (5 mu g) and 47% (10 mu g). The results indicate that 308 scFv could be utilized as an effective antiviral agent in several animal models.