PMID: 9445071Jan 28, 1998Paper

Genetic determinants responsible for acquisition of dengue type 2 virus mouse neurovirulence

Journal of Virology
M BrayC J Lai

Abstract

Studies conducted some 50 years ago showed that serial intracerebral passage of dengue viruses in mice selected for neurovirulent mutants that also exhibited significant attenuation for humans. We investigated the genetic basis of mouse neurovirulence of dengue virus because it might be directly or indirectly associated with attenuation for humans. Analysis of the sequence in the C-PreM-E-NS1 region of the parental dengue type 2 virus (DEN2) New Guinea C (NGC) strain and its mouse-adapted, neurovirulent mutant revealed that 10 nucleotide changes occurred during serial passage in mice. Seven of these changes resulted in amino acid substitutions, i.e., Leu55-Phe and Arg57-Lys in PreM, Glu71-Asp, Glu126-Lys, Phe402-Ile, and Thr454-Ile in E, and Arg105-Gln in NS1. The sequence of C was fully conserved between the parental and mutant DEN2. We constructed intertypic chimeric dengue viruses that contained the PreM-E genes or only the NS1 gene of neurovirulent DEN2 NGC substituting for the corresponding genes of DEN4. The DEN2 (PreM-E)/DEN4 chimera was neurovirulent for mice, whereas DEN2 (NS1)/DEN4 was not. The mutations present in the neurovirulent DEN2 PreM-E genes were then substituted singly or in combination into the sequence of ...Continue Reading

References

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Citations

Nov 17, 2011·Reviews in Medical Virology·Gregorius J SipsJolanda M Smit
Aug 6, 2014·Archives of Virology·Rosmari Rodriguez-RocheMaria G Guzman
Jul 30, 2015·Arquivos de neuro-psiquiatria·Marzia Puccioni-Sohler, Carolina Rosadas
Aug 21, 2007·Journal of Medical Virology·Juliano BordignonClaudia N Duarte Dos Santos
Jul 18, 2015·Genome Announcements·Felipe Scassi SalvadorCamila Malta Romano
Aug 6, 2014·The American Journal of Tropical Medicine and Hygiene·Kathryn A HanleyPreston A Marx
Dec 28, 2017·The American Journal of Tropical Medicine and Hygiene·Darci R SmithFarooq Nasar
Jan 11, 2000·Clinical Microbiology Reviews·P LeyssenJ Neyts

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