Antiretroviral agents inhibit infection of human cells by porcine endogenous retroviruses

Abstract

The efficacy of antiretroviral drugs against porcine endogenous retroviruses (PERV) that may be harbored in pig organs intended for transplantation was examined in human cells in vitro. The nucleoside analogs zidovudine and dideoxyinosine were found to effectively inhibit PERV replication.

FIG. 1

Efficacy of antiretroviral drugs against PERV in human cells. 293 cells were infected with PERV in the presence or absence of antiretroviral drugs and passaged for 3 weeks. Supernatants were assayed for the presence of PERV by RT-PCR. The doses tested were as follows: AZT, 0.01 to 10 μM; ddI, 1 to 50 μM; d4T, 50 μM; 3TC, 50 μM; indinavir, 5 to 20 μM. Each dose-response experiment was repeated at least twice; the results shown are from one representative experiment.

FIG. 2

Sequence alignment of HIV-1, MLV, and PERV. Regions of RT-flanking mutations known to confer resistance to 3TC, d4T, or ddI in HIV-1 were aligned using published sequences. (A) Protein sequence flanking the known 3TC^r mutation M184V in HIV-1. While the region is highly conserved overall between the three viruses, the M184V mutation of HIV-1 occurs naturally in both MLV and PERV (shaded box). (B) Protein sequence flanking the known ddI^r mutation L74V and the d4T^r mutation V75T. PERV and MLV sequences are identical in this region, and both viruses remain sensitive to ddI despite the presence of the L74V mutation. At position 75, the valine residue present in d4T^s HIV-1 is replaced by Q in PERV and MLV. Both viruses are d4T^r.