pubmed.ncbi.nlm.nih.gov

Design and Execution of In Vitro Polymerase Assays for Measles Virus and Related Mononegaviruses - PubMed

Design and Execution of In Vitro Polymerase Assays for Measles Virus and Related Mononegaviruses

Robert M Cox et al. Methods Mol Biol. 2024.

Abstract

Morbilliviruses such as measles virus (MeV) are responsible for major morbidity and mortality worldwide, despite the availability of an effective vaccine and global vaccination campaigns. MeV belongs to the mononegavirus order of viral pathogens that store their genetic information in non-segmented negative polarity RNA genomes. Genome replication and viral gene expression are carried out by a virus-encoded RNA-dependent RNA polymerase (RdRP) complex that has no immediate host cell analog. To better understand the organization and regulation of the viral RdRP and mechanistically characterize antiviral candidates, biochemical RdRP assays have been developed that employ purified recombinant polymerase complexes and synthetic RNA templates to monitor the initiation of RNA synthesis and RNA elongation in vitro. In this article, we will discuss strategies for the efficient expression and preparation of mononegavirus polymerase complexes, provide detailed protocols for the execution and optimization of RdRP assays, evaluate alternative options for the choice of template and detection system, and describe the application of the assay for the characterization of inhibitor candidates. Although MeV RdRP assays are the focus of this article, the general strategies and experimental approaches are readily transferable to related viruses in the mononegavirus order.

Keywords: Baculovirus expression; In vitro RNA synthesis; Insect cells; Primer extension assay; RNA-dependent RNA polymerase.

© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

PubMed Disclaimer

Similar articles

References

    1. Plemper RK, Lamb RA (2020) Paramyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM, Whelan S (eds) Fields virology, vol 1, 7th edn. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, pp 504–558
    1. Tatsuo H, Ono N, Yanagi Y (2001) Morbilliviruses use signaling lymphocyte activation molecules (CD150) as cellular receptors. J Virol 75(13):5842–5850. https://doi.org/10.1128/jvi.75.13.5842-5850.2001
    1. Muhlebach MD, Mateo M, Sinn PL, Prufer S, Uhlig KM, Leonard VH, Navaratnarajah CK, Frenzke M, Wong XX, Sawatsky B, Ramachandran S, McCray PB Jr, Cichutek K, von Messling V, Lopez M, Cattaneo R (2011) Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature 480(7378):530–533. https://doi.org/10.1038/nature10639 - DOI - PubMed - PMC
    1. Noyce RS, Bondre DG, Ha MN, Lin LT, Sisson G, Tsao MS, Richardson CD (2011) Tumor cell marker PVRL4 (nectin 4) is an epithelial cell receptor for measles virus. PLoS Pathog 7(8):e1002240. https://doi.org/10.1371/journal.ppat.1002240 - DOI - PubMed - PMC
    1. de Swart RL (2017) Measles: what we have learned from non-human primate models. Drug Discov Today Dis Model 23:31–34. https://doi.org/10.1289/ehp.1408257

MeSH terms

LinkOut - more resources