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Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation

1
Research Unit in Virology and Cancer, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico
2
Postgraduate Program in Biological Science, National Autonomous University of Mexico, 04510 Mexico City, Mexico
3
Department of Transplantation, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico
4
Department of Nephrology, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico
5
Subdirection of Diagnostic Auxiliary Services, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico
6
Department of Clinical Laboratory, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Viruses 2018, 10(12), 730; https://doi.org/10.3390/v10120730
Received: 21 September 2018 / Revised: 3 December 2018 / Accepted: 6 December 2018 / Published: 19 December 2018
(This article belongs to the Section Animal Viruses)
Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies. View Full-Text
Keywords: human herpesviruses; transplantation; coinfection; graft rejection human herpesviruses; transplantation; coinfection; graft rejection
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Sánchez-Ponce, Y.; Varela-Fascinetto, G.; Romo-Vázquez, J.C.; López-Martínez, B.; Sánchez-Huerta, J.L.; Parra-Ortega, I.; Fuentes-Pananá, E.M.; Morales-Sánchez, A. Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation. Viruses 2018, 10, 730.

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