Article Category:
Research Article

Differential Virulence and Host-Specific Fitness of Regionally Distinct Human-Derived Powassan Virus Lineage 2 Strains

Rachel E. Lange Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;
Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;

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Julia C. Pritchard Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;

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Anna S. Jaeger Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;

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Tyler D. Bold Division of Infectious Diseases and International Medicine, Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota;

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Jennifer L. White Bureau of Communicable Disease Control, New York State Department of Health, Albany, New York;

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Amy B. Dean Laboratory of Viral Diseases, New York State Department of Health, Albany, New York

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Rene C. Hull Laboratory of Viral Diseases, New York State Department of Health, Albany, New York

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Kirsten St. George Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;
Laboratory of Viral Diseases, New York State Department of Health, Albany, New York

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Alan P. Dupuis II Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;

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Matthew T. Aliota Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, Minnesota;

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Alexander T. Ciota Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, New York;
Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, New York;

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DOI:
https://doi.org/10.4269/ajtmh.24-0776
Volume/Issue:
Ahead of Print
Open access
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Powassan virus (POWV; family Flaviviridae) is a tick-borne encephalitic virus endemic to Canada, the United States, and Russia. In the United States, POWV is transmitted by ixodid ticks, and transmission foci reflect the geographic range of these vectors, primarily Ixodes scapularis. Thus, northeastern and midwestern regions of the United States contain the highest human case burdens and prevalence of infected ticks. Notably, New York (NY) and Minnesota (MN) have a long history of POWV transmission to humans. Over time, genetic divergence has occurred in these regions, giving rise to distinct midwestern and northeastern clades. Despite the established circulation of POWV, increases in reported human cases, and documented genetic distinction, an understanding of strain-specific POWV virulence is limited because of the lack of human isolates. In 2020 and 2021, two POWV strains were isolated from fatal human cases from MN (deer tick virus [DTV] MN-PV320) and NY (DTV NY21-027). Here, we provide the first characterization of geographically distinct, contemporary, human POWV isolates. Comprehensive genetic characterization was completed and phenotypic variability was determined in vitro and in vivo . Although strain fitness was similar in I. scapularis, higher mortality rates were measured in a susceptible POWV mouse model after infection with DTV NY21-027 compared with DTV MN-PV320. Genetic analysis revealed several variable amino acid substitutions, including I2173L in DTV NY21-027, which was selected for in all strains after neurological infection. These data suggest that genetic divergence of POWV strains from regionally distinct transmission foci could contribute to strain-dependent pathogenic potential in humans.

Author Notes

Financial support: This project was supported by the NIH (Grant nos. R01AI179758 and R01AI32563). This work was also supported by the NIH RNA Science and Technology in Health and Disease (Training Grant provided by the Office of Graduate Studies and the RNA Institute of the University at Albany and Grant no. F31AI176725). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the CDC, the NIH, or the Department of Health and Human Services.

Data availability: Full-genome sequences of deer tick virus (DTV) NY21-027, DTV MN-PV320, and DTV R59266 were submitted to the NIH National Center for Biotechnology Information GenBank (Accession nos. DTV NY21-027-PP151210.1, DTV MN-PV320-OL695841.1, and DTV R59266-PP151211.1). All other sequences used in this study are publicly available through GenBank (Table 2). All other datasets are contained within this publication.

Current contact information: Rachel E. Lange and Alexander T. Ciota, Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, NY, and Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, NY, E-mails: rlange@albany.edu and alexander.ciota@health.ny.gov. Julia C. Pritchard and Matthew T. Aliota, Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, MN, E-mails: pritc107@umn.edu and mtaliota@umn.edu. Anna S. Jaeger, Department of Veterinary and Biomedical Sciences, University of Minnesota Twin Cities, St. Paul, MN, and University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, E-mail: ajaeger@umn.edu. Tyler D. Bold, Division of Infectious Diseases and International Medicine, Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN, E-mail: tbold@umn.edu. Jennifer L. White, Bureau of Communicable Disease Control, New York State Department of Health, Albany, NY, E-mail: jennifer.white@health.ny.gov. Amy B. Dean and Rene C. Hull, Laboratory of Viral Diseases, New York State Department of Health, Albany, NY, E-mails: amy.dean@health.ny.gov and rene.hull@health.ny.gov. Kirsten St. George, Department of Biomedical Sciences, State University of New York University at Albany School of Public Health, Albany, NY, and Laboratory of Viral Diseases, New York State Department of Health, Albany, NY, E-mail: kirsten.st.george@health.ny.gov. Alan P. Dupuis II, Arbovirus Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, NY, E-mail: alan.dupuis@health.ny.gov

Address correspondence to Matthew T. Aliota, University of Minnesota, Department of Veterinary and Biomedical Sciences, 1971 Commonwealth Ave., Falcon Heights, MN 5510. E-mail: mtaliota@umn.edu or Alexander T. Ciota, New York State Arbovirus Laboratory, 5668 State Farm Rd., Slingerlands, NY 12159. E-mail: alexander.ciota@health.ny.gov
Copyright:
© The author(s) 2025
Received:
21 Nov 2024
|
Accepted:
03 Feb 2025
|
Published Online:
13 May 2025
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645

Leprosy

By Sir Leonard Rogers and Ernest Muir. Pp. i–xii, 1–260. Second Edition, Williams & Wilkins Co., Baltimore, Md., 1940

Goldberger on Pellagra

ed. by Milton Terris, Professor of Preventive Medicine, New York Medical College. xii + 395 pages. Louisiana State University Press, Baton Rouge, Louisiana. 1964. $12.50

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