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- Porcine endogenous retroviruses (PERVs), particularly the PERV-A/C variant, can infect human cells, posing a significant zoonotic disease risk during pig organ transplants to humans.
- The study investigates the effectiveness of Raltegravir (RAL), a viral integrase inhibitor, against PERV-A/C by employing a three-dimensional model and testing its sensitivity in vitro and in cellulo.
- Results show that RAL is an effective inhibitor of PERV-A/C integrase and replication, with IC50s achieved in the nanomolar range, highlighting its potential as a control measure for zoonotic PERV risks in xenotransplantation.
Article Abstract
Porcine endogenous retroviruses (PERVs) are present in the genomes of pig cells. The PERV-A/C recombinant virus can infect human cells and is a major risk of zoonotic disease in the case of xenotransplantation of pig organs to humans. Raltegravir (RAL) is a viral integrase (IN) inhibitor used in highly active antiretroviral treatment. In the present study, we explored the potential use of RAL against PERV-A/C. We report (i) a three-dimensional model of the PERV-A/C intasome complexed with RAL, (ii) the sensitivity of PERV-A/C IN to RAL in vitro and (iii) the sensitivity of a PERV-A/C-IRES-GFP recombinant virus to RAL in cellulo. We demonstrated that RAL is a potent inhibitor against PERV-A/C IN and PERV-A/C replication with IC50s in the nanomolar range. To date, the use of retroviral inhibitors remains the only way to control the risk of zoonotic PERV infection during pig-to-human xenotransplantation.
