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© Michaela Muller-Trutwin
HIV
Publication : Virology

AZT-resistant foamy virus

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Virology - 27 Sep 2007

Kretzschmar B, Nowrouzi A, Hartl MJ, Gärtner K, Wiktorowicz T, Herchenröder O, Kanzler S, Rudolph W, Mergia A, Wöhrl B, Rethwilm A

Link to Pubmed [PMID] – 17904181

Virology 2008 Jan;370(1):151-7

Azidothymidine (AZT) is a reverse transcriptase (RT) inhibitor that efficiently blocks the replication of spumaretroviruses or foamy viruses (FVs). To more precisely elucidate the mechanism of action of the FV RT enzyme, we generated an AZT-resistant FV in cell culture. Biologically resistant virus was obtained for simian foamy virus from macaque (SFVmac), which was insensitive to AZT concentrations of 1 mM, but not for FVs derived from chimpanzees. Nucleotide sequencing revealed four non-silent mutations in the pol gene. Introduction of these mutations into an infectious molecular clone identified all changes to be required for the fully AZT-resistant phenotype of SFVmac. The alteration of individual sites showed that AZT resistance in SFVmac was likely acquired by consecutive acquisition of pol mutations in a defined order, because some alterations on their own did not result in an efficiently replicating virus, neither in the presence nor in the absence of AZT. The introduction of the mutations into the RT of the closely related prototypic FV (PFV) did not yield an AZT-resistant virus, instead they significantly impaired the viral fitness.

http://www.ncbi.nlm.nih.gov/pubmed/17904181