Antiviral activity of an intracellularly expressed single-chain antibody fragment directed against the murine leukemia virus capsid protein

We have addressed the possibility that intracellularly expressed miniantibo dies directed against the viral capsid protein can be used as antiretrovira l agents in gene transfer experiments, R187 is a rat monoclonal antibody th at has been reported to recognize the MuLV p309(gag) capsid polypeptide, We report here that it also binds to the Pr65(gag) precursor polyprotein. R18 7 has been cloned and expressed in the form of a single-chain variable frag ment (scFv) that shows the same binding specificity as the parental antibod y. When expressed intracellularly, the R187 scFv favors the production of v iral particles showing reduced infectivity, It, however, exerts no detectab le protective effect against infection, This was observed both when using r eplication-incompetent MuLV-derived vector acid replication-competent wild- type MuLV. Although the intimate mechanism of the inhibition is not clear, this work raises the possibility that gene engineering of anti-capsid prote in scFvs may offer an additional lead for gene therapy of severe retrovirus -linked diseases.