Inactivation of respiratory syncytial virus by zinc finger reactive compounds | Boukhvalova et al. Virology Journal 2010 7 20 http content 7 1 20 VIROLOGY JOURNAL RESEARCH Open Access Inactivation of respiratory syncytial virus by zinc finger reactive compounds Marina S Boukhvalova Gregory A Prince Jorge CG Blanco Abstract Background Infectivity of retroviruses such as HIV-1 and MuLV can be abrogated by compounds targeting zinc finger motif in viral nucleocapsid protein NC involved in controlling the processivity of reverse transcription and virus infectivity. Although a member of a different viral family Pneumoviridae respiratory syncytial virus RSV contains a zinc finger protein M2-1 also involved in control of viral polymerase processivity. Given the functional similarity between the two proteins it was possible that zinc finger-reactive compounds inactivating retroviruses would have a similar effect against RSV by targeting RSV M2-1 protein. Moreover inactivation of RSV through modification of an internal protein could yield a safer whole virus vaccine than that produced by RSV inactivation with formalin which modifies surface proteins. Results Three compounds were evaluated for their ability to reduce RSV infectivity 2 2 -dithiodipyridine AT-2 tetraethylthiuram disulfide and tetramethylthiuram disulfide. All three were capable of inactivating RSV with AT-2 being the most potent. The mechanism of action of AT-2 was analyzed and it was found that AT-2 treatment indeed results in the modification of RSV M2-1. Altered intramolecular disulfide bond formation in M2-1 protein of AT-2-treated RSV virions might have been responsible for abrogation of RSV infectivity. AT-2-inactivated RSV was found to be moderately immunogenic in the cotton rats and did not cause a vaccine-enhancement seen in animals vaccinated with formalin-inactivated RSV. Increasing immunogenicity of AT-2-inactivated RSV by adjuvant Ribi however led to vaccine-enhanced disease. Conclusions This work presents evidence that compounds that inactivate .
