| 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 |
Related Documents
:
|
23569333 - Role of t cell death in maintaining immune tolerance during persistent viral hepatitis. 16990933 - Chemical synthesis of picornaviral protein primers of rna replication. 21444983 - Pandemic influenza a(h1n1) 2009 virus outbreak among boarding school pupils in madagasc... |
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: 2013-05-20 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Probing the early temporal and spatial interaction of the Sindbis virus capsid and E2 proteins with ...
Next Document: [Heart failure prevalence and predictors in Turkey: HAPPY study].