Coxsackievirus can persist in murine pancreas by deletion of 5′ terminal genomic sequences

Steven Tracy, Shane Smithee, Abdulaziz Alhazmi, Nora Chapman

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Enterovirus infections are generally acute and rapidly cleared by the host immune response. Enteroviruses can at times persist in immunologically intact individuals after the rise of the type-specific neutralizing immune response. The mechanism of enterovirus persistence was shown in group B coxsackieviruses (CVB) to be due to naturally-occurring deletions at the 5′ terminus of the genome which variably impact the stem-loop secondary structure called domain I. These deletions result in much slower viral replication and a loss of measurable cytopathic effect when such 5′ terminally deleted (TD) viruses are assayed in cell culture. The existence and persistence of CVB-TD long after the acute phase of infection has been documented in hearts of experimentally inoculated mice and naturally infected humans but to date, the existence of TD enteroviral populations have not been documented in any other organ. Enteroviral infections have been shown to impact type 1 diabetes (T1D) onset in humans as well as in the non-obese diabetic mouse model of T1D. The first step to studying the potential impact of CVB-TD on T1D etiology is to determine whether CVB-TD populations can arise in the pancreas. After inoculation of NOD diabetic mice with CVB, viral RNA persists in the absence of cytopathic virus in pancreas weeks past the acute infectious period. Analysis of viral genomic 5′ termini by RT-PCR showed CVB-TD populations displace the parental population during persistent replication in murine pancreata. J. Med. Virol. 87:240-247, 2015.

Original languageEnglish (US)
Pages (from-to)240-247
Number of pages8
JournalJournal of Medical Virology
Volume87
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Enterovirus
Pancreas
Type 1 Diabetes Mellitus
Inbred NOD Mouse
Population
Enterovirus Infections
Viruses
Human Enterovirus B
Viral RNA
Infection
Cell Culture Techniques
Genome
Polymerase Chain Reaction

Keywords

  • Coxsackievirus B3
  • Persistence
  • Terminally deleted genome
  • Type 1 diabetes

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Coxsackievirus can persist in murine pancreas by deletion of 5′ terminal genomic sequences. / Tracy, Steven; Smithee, Shane; Alhazmi, Abdulaziz; Chapman, Nora.

In: Journal of Medical Virology, Vol. 87, No. 2, 01.02.2015, p. 240-247.

Research output: Contribution to journalArticle

Tracy, Steven ; Smithee, Shane ; Alhazmi, Abdulaziz ; Chapman, Nora. / Coxsackievirus can persist in murine pancreas by deletion of 5′ terminal genomic sequences. In: Journal of Medical Virology. 2015 ; Vol. 87, No. 2. pp. 240-247.
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