Selection of single-chain antibodies that specifically interact with vesicular stomatitis virus (VSV) nucleocapsid and inhibit viral RNA synthesis

The RNA genome of non-segmented negative-strand RNA viruses is completely covered by the nucleoprotein (N) forming a ribonucleoprotein complex, the nucleocapsid. The nucleocapsid functions as the template for viral RNA synthesis that is mediated by a viral RNA-dependent RNA polymerase. It is postulated that the selection of molecules that would specifically target the nucleocapsid and thus inhibit the viral polymerase activity could represent a common approach to block negative-strand RNA viruses. Two single-chain antibody fragments (scFv) that were selected using the phage display technology and interacted specifically with vesicular stomatitis virus (VSV) nucleocapsid were characterized. The two recombinant antibodies recognize a conformational epitope on the nucleocapsid and immunoprecipitate specifically nucleocapsids from infected cell extracts. Both antibodies have a strong inhibitory effect on VSV transcription activity in vitro. Thus, they represent starting molecules for future development of in vivo viral RNA synthesis inhibitors. (c) 2005 Elsevier B.V. All rights reserved.