Retrospective detection of latent PCMV virus in donor pigs indicates no correlation with xenograft or baboon survival
Tianshu Zhang1, Avneesh Singh1, Corbin. E Goerlich1, Gheorghe Braileanu1, Alena Hershfeld1, Ivan Tatarov1, Billeta Lewis1, Faith Sentz1, Sarah Mudd1, Cinthia B Drachenberg2, David Ayares3, Bartley Griffith1, Muhammad M Mohiuddin1.
1Surgery, School of Medicine, University of Maryland, Baltimore, MD, United States; 2Pathology, School of Medicine, University of Maryland, Baltimore, MD, United States; 3Revivicor Inc, Blacksburg, VA, VA, United States
Porcine cytomegalovirus (PCMV) infection is an important concern in xenotransplantation (xTx). It has been shown that PCMV can induce endothelial cell activation, leading to a pro-coagulant state, which can cause consumptive coagulopathy and thrombotic microangiopathy in xenograft recipients. In this study, life-supporting cardiac xenotransplantation in non-human primates (NHPs, Baboons) was performed without knowing PCMV status from genetically engineered (GE) donor pigs with 7 (n=2), 9 (n=2), and 10 (n=8) gene modifications. All the recipients received anti-CD40 co-stimulation blockade-based immunosuppression. The cardiac xenograft survival in NHPs ranged from days 14 to 264. Retrospectively, GE donor pigs were tested for PCMV by sensitive PCR. Six (50%) of twelve donor pigs were positive for latent PCMV. No statistically significant difference was found in xenograft or baboon survival among PCMV-positive and negative groups. Two of six PCMV-positive cardiac xenografts were rejected and demonstrated acute cellular rejection. One of them had excessive adipose (Fat) deposition and micro and macro thrombosis, and the longest survival of the baboon was 225 days. Whereas three of six PCMV-negative cardiac xenografts were rejected and had chronic vasculopathy, the baboon's longest survival was 264 days. These results suggest that the presence or absence of PCMV in the xenograft does not affect their survival.