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Host nutritional status affects alphavirus virulence, transmission, and evolution

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dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorCarrau, Luciaen
dc.contributor.authorLevi, Laura I.en
dc.contributor.authorRezelj, Veronica V.en
dc.contributor.authorVallet, Thomasen
dc.contributor.authorBlanc, Herveen
dc.contributor.authorBoussier, Jeremyen
dc.contributor.authorMegrian, Danielaen
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorVignuzzi, Marcoen
dc.date.accessioned2020-02-07T14:34:40Zen
dc.date.available2020-02-07T14:34:40Zen
dc.date.issued2019-11en
dc.description.abstractMalnourishment, specifically overweight/obesity and undernourishment, affects more than 2.5 billion people worldwide, with the number affected ever-increasing. Concurrently, emerging viral diseases, particularly those that are mosquito-borne, have spread dramatically in the past several decades, culminating in outbreaks of several viruses worldwide. Both forms of malnourishment are known to lead to an aberrant immune response, which can worsen disease outcomes and reduce vaccination efficacy for viral pathogens such as influenza and measles. Given the increasing rates of malnutrition and spread of arthropod-borne viruses (arboviruses), there is an urgent need to understand the role of host nutrition on the infection, virulence, and transmission of these viruses. To address this gap in knowledge, we infected lean, obese, and undernourished mice with arthritogenic arboviruses from the genus Alphavirus and assessed morbidity, virus replication, transmission, and evolution. Obesity and undernourishment did not consistently influence virus replication in the blood of infected animals except for reductions in virus in obese mice late in infection. However, morbidity was increased in obese mice under all conditions. Using Mayaro virus (MAYV) as a model arthritogenic alphavirus, we determined that both obese and undernourished mice transmit virus less efficiently to mosquitoes than control (lean) mice. In addition, viral genetic diversity and replicative fitness were reduced in virus isolated from obese compared to lean controls. Taken together, nutrition appears to alter the course of alphavirus infection and should be considered as a critical environmental factor during outbreaks.en
dc.description.notesThis work was partially funded by the DARPA program PREventing EMerging Pathogenic Threats (PREEMPT) awarded to MV and JWL. Partial funding was also provided by a faculty startup package at Virginia Tech awarded to JWL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
dc.description.sponsorshipDARPA program PREventing EMerging Pathogenic Threats (PREEMPT); faculty startup package at Virginia Techen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1008089en
dc.identifier.eissn1553-7374en
dc.identifier.issn1553-7366en
dc.identifier.issue11en
dc.identifier.othere1008089en
dc.identifier.pmid31710653en
dc.identifier.urihttp://hdl.handle.net/10919/96763en
dc.identifier.volume15en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleHost nutritional status affects alphavirus virulence, transmission, and evolutionen
dc.title.serialPLOS Pathogensen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Scholarly Works, Biomedical Sciences and Pathobiology
Destination Area: Global Systems Science (GSS)