Document Detail


Relationship between within-host fitness and virulence in the vesicular stomatitis virus: correlation with partial decoupling.
MedLine Citation:
PMID:  22951843     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Given the parasitic nature of viruses, it is sometimes assumed that rates of viral replication and dissemination within hosts (within-host fitness) correlate with virulence. However, there is currently little empirical evidence supporting this principle. To test this, we quantified the fitness and virulence of 21 single- or double-nucleotide mutants of the vesicular stomatitis virus in baby hamster kidney cells (BHK-21). We found that, overall, these two traits correlated positively, but significant outliers were identified. Particularly, a single mutation in the conserved C terminus of the N nucleocapsid (U1323A) had a strongly deleterious fitness effect but did not alter or even slightly increased virulence. We also found a double mutant of the M matrix protein and G glycoprotein (U2617G/A3802G mutant) with high fitness yet low virulence. We further characterized these mutants in primary cultures from mouse brain cells and in vivo and found that their relative fitness values were similar to those observed in BHK-21 cells. The mutations had weak effects on the virus-induced death rate of total brain cells, although they specifically reduced neuron death rates. Furthermore, increased apoptosis levels were detected in neurons infected with the U2617G/A3802G mutant, consistent with its known inability to block interferon secretion. In vivo, this mutant had reduced virulence and, despite its low brain titer, it retained a relatively high fitness value owing to its ability to suppress competitor viruses. Overall, our results are in broad agreement with the notion that viral fitness and virulence should be positively correlated but show that certain mutations can break this association and that the fitness-virulence relationship can depend on complex virus-host and virus-virus interactions.
Authors:
Victoria Furió; Raquel Garijo; María Durán; Andrés Moya; John C Bell; Rafael Sanjuán
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-05
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-01-11     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12228-36     Citation Subset:  IM    
Affiliation:
Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de València, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Brain / cytology,  virology
Cell Line
Cell Membrane / metabolism
Cricetinae
Female
Glycoproteins / chemistry
Mice
Mice, Inbred BALB C
Mutation
Nucleocapsid Proteins / chemistry
Protein Structure, Tertiary
Vesicular Stomatitis / virology
Vesicular stomatitis Indiana virus / metabolism*,  pathogenicity
Virulence
Virus Replication
Grant Support
ID/Acronym/Agency:
281191//European Research Council
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Nucleocapsid Proteins
Comments/Corrections

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