Genome Number and Size Polymorphism in Zika Virus Infectious Units

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dc.contributor.authorSexton, Nicole R.en
dc.contributor.authorBellis, Eric D.en
dc.contributor.authorMurrieta, Reyes A.en
dc.contributor.authorSpangler, Mark Coleen
dc.contributor.authorCline, Parker J.en
dc.contributor.authorWeger-Lucarelli, Jamesen
dc.contributor.authorEbel, Gregory D.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-05-05T15:33:44Zen
dc.date.available2021-05-05T15:33:44Zen
dc.date.issued2021-03en
dc.description.abstractZika virus (ZIKV; Flaviviridae, Flavivirus) is an arthropod-borne infection that can result in severe outcomes, particularly in fetuses infected in utero. It has been assumed that infection by ZIKV, as well as other viruses, is largely initiated by individual virus particles binding to and entering a cell. However, recent studies have demonstrated that multiple virus particles are frequently delivered to a cell simultaneously and that this collective particle delivery enhances infection. ZIKV is maintained in nature between Aedes aegypti mosquitos and vertebrate hosts, including humans. Human infection is initiated through the injection of a relatively small initial inoculum comprised of a genetically complex virus population. Since most mutations decrease virus fitness, collective particle transmission could benefit ZIKV and other arthropod-borne diseases by facilitating the maintenance of genetic complexity and adaptability during infection or through other mechanisms. Therefore, we utilized a barcoded ZIKV to quantify the number of virus genomes that initiate a plaque. We found that individual plaques contain a mean of 10 infecting viral genomes (range, 1 to 212). Few plaques contained more than two dominant genomes. To determine whether multigenome infectious units consist of collectively transmitting virions, infectious units of ZIKV were then separated mechanically by centrifugation, and heavier fractions were found to contain more genomes per plaque-forming unit, with larger diameters. Finally, larger/heavier infectious units reformed after removal. These data suggest that ZIKV populations consist of a variety of infectious unit sizes, likely mostly made up of aggregates, and only rarely begin with a single virus genome. IMPORTANCE The arthropod-borne Zika virus (ZIKV) infects humans and can cause severe neurological sequelae, particularly in fetuses infected in utero. How this virus has been able to spread across vast geological ranges and evolve in new host populations is not yet understood. This research demonstrates a novel mechanism of ZIKV transmission through multigenome aggregates, providing insight into ZIKV evolution, immunologic evasion, and better future therapeutic design. This study shows that ZIKV plaques result from collections of genomes rather than individual genomes, increasing the potential for interactions between ZIKV genotypes.en
dc.description.notesWe thank Karolien Denef and the CSU Central Instrument Facility Core for assistance with and use of the Malvern Zetasizer Nano ZS for DLS measurements. We also thank Mark Stenglein and Marylee Kapuscinski at the CSU MIP NGS Illumina Core for assistance with MiSeq libraries. This study was supported by National Institutes of Health grants R01 AI067380 (G.D.E.), R21-AI125966 (G.D.E.), F31-AI134108 (R.A.M.), and R21-AI129593 (G.D.E.) from the National Institute of Allergy and Infectious Diseases.en
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 AI067380, R21-AI125966, F31-AI134108, R21-AI129593]; National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1128/JVI.00787-20en
dc.identifier.eissn1098-5514en
dc.identifier.issn0022-538Xen
dc.identifier.issue6en
dc.identifier.othere00787-20en
dc.identifier.pmid33328311en
dc.identifier.urihttp://hdl.handle.net/10919/103194en
dc.identifier.volume95en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectZIKVen
dc.subjectZika virusen
dc.subjectflavivirusen
dc.subjectspecific infectivityen
dc.subjectbarcoded virusen
dc.subjectaggregatesen
dc.titleGenome Number and Size Polymorphism in Zika Virus Infectious Unitsen
dc.title.serialJournal of Virologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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