Generation and characterization of genetically and antigenically diverse infectious clones of dengue virus serotypes 1-4.

TitleGeneration and characterization of genetically and antigenically diverse infectious clones of dengue virus serotypes 1-4.
Publication TypeJournal Article
Year of Publication2022
AuthorsTamura, T, Zhang, J, Madan, V, Biswas, A, Schwoerer, MP, Cafiero, TR, Heller, BL, Wang, W, Ploss, A
JournalEmerg Microbes Infect
Volume11
Issue1
Pagination227-239
Date Published2022 Dec
ISSN2222-1751
KeywordsAedes, Animals, Antibodies, Viral, Antigenic Variation, Dengue, Dengue Virus, Genetic Variation, Humans, Immunoglobulin M, Mice, Mice, Knockout, Reverse Genetics, Serogroup
Abstract

<p>Dengue is caused by four genetically distinct viral serotypes, dengue virus (DENV) 1-4. Following transmission by mosquitoes, DENV can cause a broad spectrum of clinically apparent disease ranging from febrile illness to dengue hemorrhagic fever and dengue shock syndrome. Progress in the understanding of different dengue serotypes and their impacts on specific host-virus interactions has been hampered by the scarcity of tools that adequately reflect their antigenic and genetic diversity. To bridge this gap, we created and characterized infectious clones of DENV1-4 originating from South America, Africa, and Southeast Asia. Analysis of whole viral genome sequences of five DENV isolates from each of the four serotypes confirmed their broad genetic and antigenic diversity. Using a modified circular polymerase extension reaction (CPER), we generated viruses from these isolates. The resultant clones replicated robustly in human and insect cells at levels similar to those of the parental strains. To investigate properties of these genetically diverse isolates, representative viruses from each DENV serotype were administered to NOD Rag1, IL2rg Flk2 (NRGF) mice, engrafted with components of a human immune system. All DENV strains tested resulted in viremia in humanized mice and induced cellular and IgM immune responses. Collectively, we describe here a workflow for rapidly generating infectious clones of DENV - and conceivably other RNA viruses. The infectious clones described here are a valuable resource for reverse genetic studies and for characterizing host responses to DENV and .</p>

DOI10.1080/22221751.2021.2021808
Alternate JournalEmerg Microbes Infect
PubMed ID34931940
PubMed Central IDPMC8745371
Grant ListR01 AI138797 / AI / NIAID NIH HHS / United States
R01 AI153236 / AI / NIAID NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States
R01 AI146917 / AI / NIAID NIH HHS / United States