How Does a Porcine Herpesvirus, PCMV/PRV, Induce a Xenozoonosis

TL;DR

A porcine herpesvirus, PCMV/PRV, causes severe complications in xenotransplant recipients by disrupting immune and coagulation systems, leading to a new classification as a xenozoonosis.

Contribution

The paper identifies PCMV/PRV as a xenozoonosis and reveals its impact on immune and coagulation pathways in xenotransplant recipients.

Findings

PCMV/PRV was detected in all organs of baboons and in the first human recipient of a pig heart, contributing to death.

The virus disrupts cytokine signaling and coagulation pathways without infecting primate or human cells.

Antibodies against HHV-6 cross-react with PCMV/PRV and may offer protection in humans.

Abstract

Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), a porcine herpesvirus, has been shown to significantly reduce the survival time of porcine xenotransplants in non-human primates. The virus was detected in all the examined organs of baboons transplanted with PCMV/PRV-positive organs and it was also transmitted to the first human recipient of a pig heart, contributing to the patient’s death. PCMV/PRV induces consumptive coagulopathy and thrombocytopenia in xenotransplant recipients. Initial studies in baboons revealed that the virus triggered increased release of tumor necrosis factor α (TNFα) and interleukin 6 (IL-6), along with elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) complexes. Since there is no evidence that PCMV/PRV infects primate cells, including human cells, the virus appears to directly interact with immune and endothelial cells, disrupting cytokine signaling and coagulation pathways. The highest viral load was detected in the explanted pig heart, suggesting active replication at this site. Additionally, cells expressing PCMV/PRV proteins were identified in all the examined baboon organs, where pig cells were also found. Since PCMV/PRV affects only xenotransplant recipients and not healthy humans, this condition should be classified as a xenozoonosis. Interestingly, antibodies against human herpesvirus 6 (HHV-6) cross-react with PCMV/PRV and may contribute to protection against infection in humans. Further research is needed to uncover the molecular mechanisms underlying this xenozoonotic disease.

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