Commentary: Limitations of using oral fluids to monitor PCMV/PRV infections in pigs for xenotransplantation

Joachim Denner^*

• Institute of Virology, Department of Veterinary Medicine, Free University of Berlin, Berlin, Germany

To address the shortage of human tissues and organs for treating organ failure, xenotransplantation is progressing toward clinical application. Pigs have been chosen as the donor species for various reasons, and extensive genetic modifications are being implemented to prevent xenotransplant rejection. However, xenotransplantation may be associated with transmission of pathogenic pig microorganisms. One such pathogen is the porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), which has been shown to significantly reduce the survival time of pig organs in non-human primates [1]. Although originally named PCMV because of the morphological similarities between infected cells and those infected with human cytomegalovirus (HCMV), subsequent research revealed that PCMV/PRV is actually a roseolovirus related to human herpesviruses 6 and 7, not HCMV. The International Committee on Taxonomy of Viruses (ICTV) has officially designated the virus as suid herpesvirus 2 (SuHV-2). This virus was also transmitted to the first human recipient of a genetically modified pig heart and contributed to his death [2]. The virus had not been detected in the donor pig of the transplanted heart due to the use of an inappropriate detection method. A nasal swab from this donor pig has been tested using PCR; however, virus can be detected using nasal swabs only in newly infected animals experiencing rhinitis [3]. In one experiment infecting pigs with PCMV/PRV, the maximum duration of nasal virus excretion was recorded at 32 days [4]. Therefore, for future clinical xenotransplantations, it is essential to implement highly sensitive and appropriate detection methods.Recently, Schommer et al. [5] investigated the feasibility of using oral fluids and real-time PCR for PCMV/PRV screening. After screening animals from the National Swine Research and Resource Center herd using spleen tissue, blood, and oral fluids, they concluded that oral fluid testing could be used to monitor xenotransplant donor herds for PCMV/PRV.The study by Schommer et al. [5] makes a significant contribution to the development of efficient detection strategies 59 for PCMV/PRV, particularly through the use of non-invasive samples from pigs. Oral fluids, which are easier to collect 60 than oral or saliva swabs, would be an ideal sample for these purposes. I agree that herd monitoring using oral fluids can 61 be convenient, such as utilizing a single rope to collect samples from multiple animals. However, the results indicate that 62 this strategy is insufficient, particularly for adult pigs. While this method may be suitable for very young piglets, capturing 63 them and collecting oral swabs would be a more effective approach to obtaining individual results. In all other cases this 64 method has to be combined with immunological testing. Especially in adult animals, where the virus is typically in its latent 65 phase, screening with oral fluids or swabs will consistently yield false-negative results, as demonstrated in previous studies 66 [6,8]. Therefore, oral fluid or swabs testing should always be complemented by immunological testing to ensure accurate