A single nucleotide change in the mumps virus F gene affects virus fusogenicity in vitro and virulence in vivo
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Mumps virus is highly neurotropic, with evidence of infection of the central nervous system in more than half of clinical cases. In the prevaccine era, mumps was a major cause of viral meningitis in most developed countries. Despite efforts to attenuate the virus, some mumps vaccines have retained virulence properties and have caused aseptic meningitis in vaccinees, resulting in public resistance to vaccination in some countries. Ensuring the safety of mumps vaccines is an important public health objective, as the need for robust immunization programs has been made clear by the recent resurgence of mumps outbreaks worldwide, including the United States, which in 2006 experienced its largest mumps outbreak in 20 years. To better understand the molecular basis of mumps virus attenuation, the authors developed two infectious full-length cDNA clones for a highly neurovirulent strain of mumps virus. The clones differed at only one site, possessing either an A or G at nucleotide position 271 in the F gene, to represent the heterogeneity identified in the original virulent clinical isolate. In comparison to the clinical isolate, virus rescued from the A-variant cDNA clone grew to higher cumulative titers in vitro but exhibited similar cytopathic effects in vitro and virulence in vivo. In contrast, virus rescued from the G-variant cDNA clone, in comparison to the clinical isolate and the A-variant, was more fusogenic in vitro but replicated to lower cumulative titers and was less neurovirulent in vivo. These data suggest that nucleotide position 271 in the F gene plays a significant role in virus pathogenesis. This infectious clone system will serve as a key tool for further examination of the molecular basis for mumps virus neurovirulence and neuroattenuation.
- Afzal MA, Marsden S, Hull RM, Pipkin PA, Bently ML, Minor PD (1999). Evaluation of the neurovirulence test for mumps vaccines. Biologicals 27: 43–49. CrossRef
- Amexis G, Rubin S, Chatterjee N, Carbone K, Chumakov K (2003). Identification of a new genotype H wild-type mumps virus strain and its molecular relatedness to other virulent and attenuated strains. J Med Virol 70: 284–286. CrossRef
- Arruda WO, Kondageski C (2001). Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Parana, Brazil, 1998. Rev Inst Med Trop Sao Paulo 43: 301–302.
- Bang HO, Bang J (1943). Involvement of the central nervous system in mumps. Acta Med Scand 113: 487–505. CrossRef
- Brown EG, Furesz J, Dimock K, Yarosh W, Contreras G (1991). Nucleotide sequence analysis of Urabe mumps vaccine strain that caused meningitis in vaccine recipients. Vaccine 9: 840–842. CrossRef
- Buchholz UJ, Finke S, Conzelmann KK (1999). Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol 73: 251–259.
- Carbone KM, Rubin. (2007) Mumps virus. In: Fields virology. Knipe DM, Howley PM (eds). Philadelphia: Wolters Kluwer, Lippinocott Williams & Wilkins, pp 1527–1542.
- Castilla J, Garcia CM, Barricarte A, Irisarri F, Nunez-Cordoba JM, Barricarte A (2007). Mumps outbreak in Navarre region, Spain, 2006–2007. Euro Surveill 12: E070215.
- Centers for Disease Control and Prevention (2006a). Brief report: update: mumps activity—United States, January 1–October 7, 2006. MMWR Morb Mortal Wkly Rep 55: 1152–1153.
- Centers for Disease Control and Prevention (CDC) (2006b). Mumps epidemic—United Kingdom, 2004–2005. MMWR Morb Mortal Wkly Rep 55: 173–175.
- Clarke DK, Sidhu MS, Johnson JE, Udem SA (2000). Rescue of mumps virus from cDNA. J Virol 74: 4831–4838. CrossRef
- Elango N, Varsanyi TM, Kovamees J, Norrby E (1988). Molecular cloning and characterization of six genes, determination of gene order and intergenic sequences and leader sequence of mumps virus. J Gen Virol 69: 2893–2900. CrossRef
- Kojouharova M, Kurchatova A, Marinova L, Georgieva T (2007). Mumps outbreak in Bulgaria, 2007: a preliminary report. Euro Surveill 12: E070322.
- Lemon K, Rima BK, McQuaid S, Allen IV, Duprex WP (2007). The F gene of rodent brain-adapted mumps virus is a major determinant of neurovirulence. J Virol 81: 8293–8302. CrossRef
- Love A, Rydbeck R, Ljungdahl A, Kristensson K, Norrby E (1986). Selection of mutants of mumps virus with altered structure and pathogenicity in vivo. Microb Pathogen 1: 149–158. CrossRef
- Malik T, Wolbert C, Mauldin J, Sauder C, Carbone K, Rubin S (2007). Functional consequences of attenuating mutations in the hemagglutinin-neuraminidase, fusion and polymerase proteins of a wild type mumps virus strain. J Gen Virol 83: 2533–2541. CrossRef
- Miller E, Goldacre M, Pugh S, Colville A, Farrington P, Flower A, Nash J, MacFarlane L, Tettmar R (1993). Risk of aseptic meningitis after measles, mumps and rubella vaccine in UK children. Lancet 341: 979–982. CrossRef
- Paterson RG, Lamb RA (1990). RNA editing by G-nucleotide insertion in mumps virus P-gene mRNA transcripts. J Virol 64: 4137–4145.
- Rubin SA, Afzal MA, Powell CL, Bentley ML, Auda GR, Taffs RE, Carbone KM (2005). The rat-based neurovirulence safety test for the assessment of mumps virus neurovirulence in humans: an international collaborative study. J Infect Dis 191: 1123–1128. CrossRef
- Rubin SA, Pletnikov M, Taffs R, Snoy PJ, Kobasa D, Brown EG, Wright KE, Carbone KM (2000). Evaluation of a neonatal rat model for prediction of mumps virus neurovirulence in humans. J Virol 74: 5382–5384. CrossRef
- Rubin SA, Snoy P, Wright KE, Brown EG, Reeve P, Beeler JA, Carbone KM (1999). The mumps virus neurovirulence safety test in rhesus monkeys: a comparison of mumps virus strains. J Infect Dis 180: 521–525. CrossRef
- Schmid D, Pichler AM, Wallenko H, Holzmann H, Allerberger F (2006). Mumps outbreak affecting adolescents and young adults in Austria, 2006. Euro Surveill, 11, E060615.
- Spanaki A, Hajiioannou J, Varkarakis G, Antonakis T, Kyrmizakis DE (2007). Mumps epidemic among young British citizens on the island of Crete. Infection 35: 104–106. CrossRef
- Sugiura A, Yamada A (1991). Aseptic meningitis as a complication of mumps vaccination. Pediatr Infect Dis J 10: 209–213. CrossRef
- Szomor K, Molnar Z, Huszti G, Ozsvarne CE (2007). Local mumps outbreak in Hungary, 2007. Euro Surveill 12: E070329.
- Tesovic G, Lesnikar V (2006). Aseptic meningitis after vaccination with L-Zagreb mumps strain—virologically confirmed cases. Vaccine 24: 6371–6373. CrossRef
- Weibel RE, Buynak EB, McLean AA, Hilleman MR (1979). Follow-up surveillance for antibody in human subjects following live attenuated measles, mumps, and rubella virus vaccines. Proc Soc Exp Biol Med 162: 328–332.
- A single nucleotide change in the mumps virus F gene affects virus fusogenicity in vitro and virulence in vivo
Journal of NeuroVirology
Volume 13, Issue 6 , pp 513-521
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- infectious clone system
- reverse genetics
- Industry Sectors