Susceptibility of recombinant porcine endogenous retrovirus reverse transcriptase to nucleoside and non-nucleoside inhibitors.
Transplantation of organs, tissues or cells from pigs to humans could be a potential solution to the shortage of human organs for transplantation. Porcine endogenous retroviruses (PERVs) remain a major safety concern for porcine xenotransplantation. Thus, finding drugs that could be used as virological prophylaxis (or therapy) against PERV replication would be desirable. One of the most effective ways to block retroviral multiplication is to inhibit the enzyme reverse transcriptase (RT) which catalyzes the reverse transcription of viral RNA to proviral double-stranded DNA. We report here the cloning and expression of PERV RT and its susceptibility to several inhibitors. Our data demonstrate PERV susceptibility in vitro to the triphosphorylated nucleoside analog of zidovudine (AZT) and to ddGTP and to a lesser extent to ddTTP but almost no susceptibility to the non-nucleoside RT inhibitors tested.
Wilhelm
M
M
Institut de Biologie Moléculaire et Cellulaire, 15, rue René Descartes, 67084 Strasbourg, France. wilhelm@ibmc.u-strasbg.fr
Fishman
J A
JA
Pontikis
R
R
Aubertin
A M
AM
Wilhelm
F X
FX
D000595:Amino Acid Sequence; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003001:Cloning, Molecular; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000201:enzymology*; D006801:Humans; D015636:Magnesium Chloride / Q000378:metabolism; D017895:Manganese Compounds / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D016914:Ribonuclease H / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism; D013552:Swine
D002712:Chlorides; D017895:Manganese Compounds; D009705:Nucleosides; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D015636:Magnesium Chloride; D012965:Sodium Chloride; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase; D016914:Ribonuclease H; C025340:manganese chloride