Document Detail


Prevalent human coxsackie B-5 virus infects porcine islet cells primarily using the coxsackie-adenovirus receptor.
MedLine Citation:
PMID:  15479464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We have previously demonstrated that transplanting porcine encephalomyocarditis virus (EMCV)-infected porcine islet cells (PICs) results in transmission of the virus to recipient mice, which is manifested by acute fatal infection within 5 to 8 days. Here, we determined PIC susceptibility to a related and highly prevalent human picornavirus, coxsackie B-5 virus (CVB-5). METHODS: PICs were inoculated with CVB-5 in vitro for up to 96 hours and infectivity, level of virus replication, and cellular function determined. Subsequently, monoclonal and polyclonal antibody blocking experiments were used to investigate the receptor CVB-5 uses to enter PICs, and the ability of CVB-5-infected islets to reverse diabetes analyzed in mice. RESULTS: Adult pig islets inoculated with CVB-5 in vitro showed a typical picornaviral replication cycle with a 2-h lag phase followed by a 4-h exponential phase during which the virus titer increased by 4 logs. However, CVB-5 was less cytolytic to PICs than EMCV, resulting in a persistent productive infection lasting for up to 96 h, with minimal evidence of cell lysis. Double immunostaining confirmed the presence of CVB-5 antigens in insulin-producing islets. Infection of PICs in the presence of antibodies against human coxsackie-adenovirus receptor (CAR) resulted in near complete blockage in production of infectious virus particles whereas blocking with anti-porcine decay-accelerating factor (DAF, also called CD55) or anti-porcine membrane cofactor protein (MCP, also called CD46) only slightly decreased the number of infectious CVB-5 particles produced. Immunofluoresence staining showed CAR and MCP expression on the islet surface, but not DAF. Transplanting CVB-5-infected PICs into diabetic C57BL/6 mice resulted in reversal of diabetes. CONCLUSION: Although PICs are susceptible to human CVB-5, the infection does not appear to affect xenograft function in vitro or in vivo in the short term.
Authors:
Suzanne E Myers; Laurie Brewer; Daniel P Shaw; Wallace H Greene; Brenda C Love; Bernhard Hering; O Brad Spiller; M Kariuki Njenga
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Xenotransplantation     Volume:  11     ISSN:  0908-665X     ISO Abbreviation:  Xenotransplantation     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-13     Completed Date:  2005-03-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9438793     Medline TA:  Xenotransplantation     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  536-46     Citation Subset:  IM    
Affiliation:
Pathobiology Graduate Program, Veterinary Science Department, Pennsylvania State University, University Park, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal
Antibodies, Viral / blood
Diabetes Mellitus, Experimental / therapy*
Enterovirus B, Human / isolation & purification*
Enterovirus Infections / epidemiology*
Humans
Islets of Langerhans / virology*
Islets of Langerhans Transplantation*
Mice
Mice, Inbred C57BL
Neutralization Tests
Receptors, Virus / immunology,  metabolism
Risk Factors
Seroepidemiologic Studies
Swine
Transplantation, Heterologous*
Grant Support
ID/Acronym/Agency:
HL04369/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Viral; 0/Receptors, Virus; 0/adenovirus receptor

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