Expression of recipient cytomegalovirus in immunosuppressed and xenotransplanted Macaca fascicularis may be related to more severe gastrointestinal lesions

Laura Cavicchioli, Rossella Zanetti, Serena Ferraresso, Claire Crossan, Peter A Barry, Massimo Boldrin, Marta Vadori, Silvia Ferro, Fiorella Calabrese, Linda Scobie, Emanuele Cozzi, Valentina Zappulli

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background Xenotransplantation is a potential answer to the current organ shortage, but the risk of infections related to overimmunosuppression is an important parameter that may predict the recipient's long-term survival. Cytomegalovirus (CMV) in xenotransplanted and immunosuppressed primates is a well-known cause of disease particularly affecting the gastrointestinal (GI) tract and a zoonotic concern. Methods Post-mortem sera and tissues from 45 immunosuppressed and xenografted Macaca fascicularis were evaluated for CMV using antisera specific for the immediate early 1 (IE1), anti-RhCMV, and QPCR for virus. Results Serological analysis showed 100% positivity for the presence of CMV antibodies following the application of a specific test designed for RhCMV. Five of 45 primates showed typical lesions of CMV infection in the GI tract, including neutrophilic enteritis and inclusion bodies. Molecular analysis confirmed the presence of recipient's CMV in the tissues with CMV histopathology. Porcine CMV from the donor animals was not found in any of the CMV-specific IHC-positive recipients. Conclusion The presence of active CMV infection in animals intended for xenograft experiments can lead to severe gastrointestinal lesions that could impact the overall aims of the study. In such cases, the animals should be investigated using appropriate (non-human primate-specific) diagnostic tools prior to use and treated aggressively with state-of-the-art antiviral therapy.

Original languageEnglish (US)
Pages (from-to)135-143
Number of pages9
JournalXenotransplantation
Volume22
Issue number2
DOIs
StatePublished - Mar 1 2015

Fingerprint

Macaca fascicularis
Cytomegalovirus
Primates
Cytomegalovirus Infections
Gastrointestinal Tract
Art Therapy
Heterologous Transplantation
Enteritis
Inclusion Bodies
Zoonoses
Heterografts
Antiviral Agents
Immune Sera
Swine
Viruses
Antibodies
Infection
Serum

Keywords

  • cytomegalovirus
  • gastrointestinal
  • immunohistochemistry
  • immunosuppression
  • primates
  • xenotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Expression of recipient cytomegalovirus in immunosuppressed and xenotransplanted Macaca fascicularis may be related to more severe gastrointestinal lesions. / Cavicchioli, Laura; Zanetti, Rossella; Ferraresso, Serena; Crossan, Claire; Barry, Peter A; Boldrin, Massimo; Vadori, Marta; Ferro, Silvia; Calabrese, Fiorella; Scobie, Linda; Cozzi, Emanuele; Zappulli, Valentina.

In: Xenotransplantation, Vol. 22, No. 2, 01.03.2015, p. 135-143.

Research output: Contribution to journalArticle

Cavicchioli, L, Zanetti, R, Ferraresso, S, Crossan, C, Barry, PA, Boldrin, M, Vadori, M, Ferro, S, Calabrese, F, Scobie, L, Cozzi, E & Zappulli, V 2015, 'Expression of recipient cytomegalovirus in immunosuppressed and xenotransplanted Macaca fascicularis may be related to more severe gastrointestinal lesions', Xenotransplantation, vol. 22, no. 2, pp. 135-143. https://doi.org/10.1111/xen.12153
Cavicchioli, Laura ; Zanetti, Rossella ; Ferraresso, Serena ; Crossan, Claire ; Barry, Peter A ; Boldrin, Massimo ; Vadori, Marta ; Ferro, Silvia ; Calabrese, Fiorella ; Scobie, Linda ; Cozzi, Emanuele ; Zappulli, Valentina. / Expression of recipient cytomegalovirus in immunosuppressed and xenotransplanted Macaca fascicularis may be related to more severe gastrointestinal lesions. In: Xenotransplantation. 2015 ; Vol. 22, No. 2. pp. 135-143.
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abstract = "Background Xenotransplantation is a potential answer to the current organ shortage, but the risk of infections related to overimmunosuppression is an important parameter that may predict the recipient's long-term survival. Cytomegalovirus (CMV) in xenotransplanted and immunosuppressed primates is a well-known cause of disease particularly affecting the gastrointestinal (GI) tract and a zoonotic concern. Methods Post-mortem sera and tissues from 45 immunosuppressed and xenografted Macaca fascicularis were evaluated for CMV using antisera specific for the immediate early 1 (IE1), anti-RhCMV, and QPCR for virus. Results Serological analysis showed 100{\%} positivity for the presence of CMV antibodies following the application of a specific test designed for RhCMV. Five of 45 primates showed typical lesions of CMV infection in the GI tract, including neutrophilic enteritis and inclusion bodies. Molecular analysis confirmed the presence of recipient's CMV in the tissues with CMV histopathology. Porcine CMV from the donor animals was not found in any of the CMV-specific IHC-positive recipients. Conclusion The presence of active CMV infection in animals intended for xenograft experiments can lead to severe gastrointestinal lesions that could impact the overall aims of the study. In such cases, the animals should be investigated using appropriate (non-human primate-specific) diagnostic tools prior to use and treated aggressively with state-of-the-art antiviral therapy.",
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AU - Crossan, Claire

AU - Barry, Peter A

AU - Boldrin, Massimo

AU - Vadori, Marta

AU - Ferro, Silvia

AU - Calabrese, Fiorella

AU - Scobie, Linda

AU - Cozzi, Emanuele

AU - Zappulli, Valentina

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AB - Background Xenotransplantation is a potential answer to the current organ shortage, but the risk of infections related to overimmunosuppression is an important parameter that may predict the recipient's long-term survival. Cytomegalovirus (CMV) in xenotransplanted and immunosuppressed primates is a well-known cause of disease particularly affecting the gastrointestinal (GI) tract and a zoonotic concern. Methods Post-mortem sera and tissues from 45 immunosuppressed and xenografted Macaca fascicularis were evaluated for CMV using antisera specific for the immediate early 1 (IE1), anti-RhCMV, and QPCR for virus. Results Serological analysis showed 100% positivity for the presence of CMV antibodies following the application of a specific test designed for RhCMV. Five of 45 primates showed typical lesions of CMV infection in the GI tract, including neutrophilic enteritis and inclusion bodies. Molecular analysis confirmed the presence of recipient's CMV in the tissues with CMV histopathology. Porcine CMV from the donor animals was not found in any of the CMV-specific IHC-positive recipients. Conclusion The presence of active CMV infection in animals intended for xenograft experiments can lead to severe gastrointestinal lesions that could impact the overall aims of the study. In such cases, the animals should be investigated using appropriate (non-human primate-specific) diagnostic tools prior to use and treated aggressively with state-of-the-art antiviral therapy.

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