Cellular mechanisms account for decreased anti-HIV-1 activity of nucleoside analogs. NLM AIDSLINE Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

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Cellular mechanisms account for decreased anti-HIV-1 activity of nucleoside analogs.

Abstr Gen Meet Am Soc Microbiol. 1994;94:484 (abstract no. T-14). Unique Identifier : AIDSLINE ASM94/94313090
Doerr HW; Cinatl J Jr; Weber B; Cinatl J; Department of Medical Virology, J.W. Goethe University,; Frankfurt/M, Federal Republic of Germany.

Abstract: We tested whether cellular mechanisms (cell resistance) may account for decreased anti-HIV-1 activity of nucleoside analogs. For this aim several MOLT-4 cell sublines were established which exerted resistance against toxic effects of nucleoside analogs including AZT, ddI or ddC and MOLT-4 subline resistant to different cytotoxic agents (e.g. vincristine, daunomycin) so-called multidrug resistance. The results showed that anti-HIV-1 activities of AZT, ddI and ddC were significantly decreased in MOLT-4 sublines resistant to the respective nucleoside kinases. In the multidrug resistant MOLT-4 subline which expressed high levels of P-glycoprotein significantly decreased anti-HIV-1 activities of AZT and ddI were demonstrated. This effect was associated with decreased accumulation of the nucleoside analogs in the multidrug resistant cells. Our in vitro results showed that different cellular mechanisms (other than virus itself) may account for failure of nucleoside analogs to inhibit efficiently HIV replication.
Keywords: Carrier Proteins/BIOSYNTHESIS Cell Line Didanosine/*TOXICITY Drug Resistance Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY Membrane Glycoproteins/BIOSYNTHESIS Tumor Cells, Cultured Virus Replication/*DRUG EFFECTS Zalcitabine/*TOXICITY Zidovudine/*TOXICITY ABSTRACTKWDcarrierproteins/biosynthesiscelllinedidanosine/KWDtoxicitydrugresistancehumanhiv-1/KWDdrugeffects/physiologymembraneglycoproteins/biosynthesistumorcells,culturedvirusreplication/KWDdrugeffectszalcitabine/KWDtoxicityzidovudine/KWDtoxicityabstract
941030
M94A0864

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