Transmission of Porcine Endogenous Retrovirus Produced from Different Recipient Cells In Vivo

Abstract

Humanized pigs have been developed to reduce the incidence of immune rejection in xenotransplantation, but significant concerns remain, such as transmission of viral zoonosis. Porcine endogenous retroviruses (PERV), which exist in the genome of pigs, are produced as infectious virions from all porcine cells and cause zoonosis. Here, we examined the possibility of zoonosis of hosts under conditions of immune suppression or xenotransplantation of cells producing host-adapted viruses. Upon transplantation of PERV-producing porcine cells into mice, no transmission of PERV was detected, whereas, transmission of PERV from mice transplanted with mouse-adapted PERV-producing cells was detected. In addition, the frequency of PERV transmission was increased in CsA treated mice transplanted with PERV-producing murine cells, compared with PERV-producing porcine cells. Transmission of PERV to host animals did not affect weight but immune responses, in particular, the number of T cells from PERV-transmitted mice, were notably reduced. The observed risk of PERV zoonosis highlights the requirement for thorough evaluation of viral zoonosis under particular host conditions, such as immunosuppressive treatment and transplantation with host-adapted virus-producing cells.

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“…For example, a higher transmission of PERV has been observed in mice xenografted with PERV-producing cells, in particular under an immunosuppressant treatment. Also, this PERV infection was correlated with a decrease of T cells proportion, especially CD4+ subset ( Kim et al, 2016 ). In addition, SLC52A1 and SLC52A2 molecules are described as receptors for PERV-A particles on human cells in vitro ( Colon-Moran et al, 2017 ), providing a demonstration of a possible infection of human cells by PERVs.…”

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“…Retroviral genomes become integrated into the genome of infected germ cells and thus they are detected in organs and tissues, which can be used for xenotransplantation (Acharya et al, 2019). This genus included mainly Porcine-type-C oncovirus species and cause malignant disease in animals and humans as shown in vitro by Acharya et al (2019); similarly Kim et al (2016) reported that viral zoonosis occurred under particular host conditions, such as immunosuppressive treatment and transplantation with hostadapted virus-producing cells, and thus transmission of PERV was created from different recipient cells in vivo. However, the in-vivo studies by Denner (2018) showed that PERV transmission has not been observed in any of the many preclinical and clinical xenotransplantation trials performed so far, and not in any of the many experimental PERV-infection experiments.…”

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“…A previous report by our group showed PERV transmission from mice transplanted with mouse-adapted PERV-producing cells. In addition, the frequency of PERV transmission was increased in CsA-treated mice transplanted with PERV-producing murine cells, compared to PERV-producing porcine cells [21].…”

“…In order to prevent acute immune rejection, a large amount of immunosuppressive drug is prescribed and continuous administration is required. Although long-term survival has become possible with the prescription of immunosuppressive drugs after interspecies transplantation, it has the risk of chronic immunosuppression-related infection, xenograft rejection, and host adaptive virus production [17,18,19,20,21].…”