Document Detail


Pathogenesis of coxsackievirus-B5 acquired from intra-renal porcine islet cell xenografts in diabetic mice.
MedLine Citation:
PMID:  19392724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We previously demonstrated the ability of a human isolate of coxsackievirus-B5 (CVB5) to infect productively adult porcine islet cells (PICs) in vitro. PICs infected with CVB5 remain viable, and upon transplantation reversed diabetes in C56BL/6 mice for up to 5 days. METHODS: In the present work, we expanded this graft-to-host xenozoonosis model by examining the long-term functionality of CVB5-infected PIC xenografts in immunosuppressed mice. And, we characterized the pathogenesis of CVB5 infection in mice resulting from directional transmission of the virus from PIC xenografts to surrounding tissues in a mouse model for immunosuppressed human PIC xenograft recipients. RESULTS: Both acutely (12 h) and chronically (72 h) infected PIC xenografts functioned in vivo to reverse diabetes in mice. The efficacy of both infected and un-infected PICs was transient beyond 5 days post-inoculation and the long-term functionality of the grafts was compromised by host-to-graft rejection. CVB5-infected PIC xenografts transmitted infectious virus to immunosuppressed recipient mice resulting in extensive histopathologic changes. The virus replicated in the heart, liver, spleen, kidney, pancreas, brain and skeletal muscle in higher levels in severe-combined immunodeficient (SCID) mice that were directly inoculated with virus when compared to controls. In addition, infectious virus was recovered for up to 22 days after inoculation in SCID mice whereas it was only detected up to Day 4 PI in non-SCID mice. CONCLUSIONS: Immunosuppressed PIC xenograft recipients may be more susceptible to infection with CVB5 which could target the xenograft leading to disseminated infection in the host.
Authors:
Suzanne E Myers; Rebecca LaRue; Daniel P Shaw; Brenda C Love; Kariuki Njenga M; Moses K Njenga
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Xenotransplantation     Volume:  16     ISSN:  1399-3089     ISO Abbreviation:  Xenotransplantation     Publication Date:    2009 Mar-Apr
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-05-28     Revised Date:  2010-10-25    
Medline Journal Info:
Nlm Unique ID:  9438793     Medline TA:  Xenotransplantation     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  91-8     Citation Subset:  IM    
Affiliation:
Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA. seb116@psu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Coxsackievirus Infections / transmission*
Diabetes Mellitus, Experimental / therapy
Enterovirus B, Human / metabolism,  pathogenicity*
Humans
Islets of Langerhans Transplantation* / adverse effects
Kidney / cytology,  pathology
Mice
Mice, Inbred C57BL
Mice, SCID
Swine
Transplantation, Heterologous / adverse effects*
Virus Replication
Grant Support
ID/Acronym/Agency:
HL 04369./HL/NHLBI NIH HHS; K01 HL004369-04/HL/NHLBI NIH HHS
Comments/Corrections
Erratum In:
Xenotransplantation. 2009 May;16(3):192
Note: Njenga, Moses K [corrected to M, Kariuki Njenga]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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