A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies

Cynthia Besch-Williford, Patricia Pesavento, Shari Hamilton, Beth Bauer, Beatrix Kapusinszky, Tung Phan, Eric Delwart, Robert Livingston, Susan Cushing, Rie Watanabe, Stephen Levin, Diana Berger, Matthew Myles

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.

Original languageEnglish (US)
Pages (from-to)596-603
Number of pages8
JournalToxicologic Pathology
Volume45
Issue number5
DOIs
StatePublished - Jul 1 2017

Fingerprint

Polyomavirus
Rats
Epidemiologic Studies
Polymerase chain reaction
Tissue
Interleukin-2 Receptors
Polyomavirus Infections
Viruses
Nude Rats
Nucleic Acids
Intranuclear Inclusion Bodies
Metagenomics
Respiratory Mucosa
Assays
Lacrimal Apparatus
Polymerase Chain Reaction
Genes
Inbred F344 Rats
Salivary Glands
Respiratory System

Keywords

  • exocrine glands
  • immunodeficiency
  • next-generation sequencing
  • rat pathology
  • rat polyomavirus 2
  • reproductive system
  • respiratory system

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

Cite this

A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats : Characterization, Transmission, and Preliminary Epidemiologic Studies. / Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew.

In: Toxicologic Pathology, Vol. 45, No. 5, 01.07.2017, p. 596-603.

Research output: Contribution to journalArticle

Besch-Williford, C, Pesavento, P, Hamilton, S, Bauer, B, Kapusinszky, B, Phan, T, Delwart, E, Livingston, R, Cushing, S, Watanabe, R, Levin, S, Berger, D & Myles, M 2017, 'A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies', Toxicologic Pathology, vol. 45, no. 5, pp. 596-603. https://doi.org/10.1177/0192623317723541
Besch-Williford, Cynthia ; Pesavento, Patricia ; Hamilton, Shari ; Bauer, Beth ; Kapusinszky, Beatrix ; Phan, Tung ; Delwart, Eric ; Livingston, Robert ; Cushing, Susan ; Watanabe, Rie ; Levin, Stephen ; Berger, Diana ; Myles, Matthew. / A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats : Characterization, Transmission, and Preliminary Epidemiologic Studies. In: Toxicologic Pathology. 2017 ; Vol. 45, No. 5. pp. 596-603.
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