Efficacy of antiretroviral agents against murine replication-competent retrovirus infection in human cells.
Retroviral vectors for gene therapy are designed to minimize the occurrence of replication-competent retrovirus (RCR); nonetheless, it is possible that a vector-derived RCR could establish an infection in a patient. Since the efficacy of antiretroviral agents can be impacted by interactions between virus, host cell, and drug, five commonly used antiretroviral drugs were evaluated for their abilities to inhibit the replication of a murine leukemia virus (MLV)-derived RCR in human cells. The results obtained indicate that the combination of nucleoside analogs zidovudine and dideoxyinosine with the protease inhibitor indinavir effectively inhibits MLV-derived RCR replication in three human cell lines. In addition, MLV-derived RCR was found to be inherently resistant to the nucleoside analogs lamivudine and stavudine, suggesting that mutations conferring resistance to nucleoside analogs in human immunodeficiency virus type 1 have the same effect even in an alternative viral backbone.
Powell
S K
SK
Genetic Therapy, Inc., a Novartis Company, Gaithersburg, Maryland 20878, USA. sharon.powell@pharma.novartis.com
Artlip
M
M
Kaloss
M
M
Brazinski
S
S
Lyons
R
R
McGarrity
G J
GJ
Otto
E
E
D002460:Cell Line; D016049:Didanosine / Q000494:pharmacology; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects; D006801:Humans; D019469:Indinavir / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000187:drug effects / Q000502:physiology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019469:Indinavir; D016049:Didanosine