Molecular mechanisms of HIV-1 resistance to nucleoside reverse transcriptase inhibitors (NRTIs).

Abstract:

Nucleoside reverse transcriptase inhibitors (NRTIs), such as 3'-azido-3'-deoxythymidine, 2',3'-dideoxyinosine and 2',3'-dideoxy-3'-thiacytidine, are effective inhibitors of human immunodeficiency type 1 (HIV-1) replication. NRTIs are deoxynucleoside triphosphate analogs, but lack a free 3'-hydroxyl group. Once NRTIs are incorporated into the nascent viral DNA, in reactions catalyzed by HIV-1 reverse transcriptase (RT), further viral DNA synthesis is effectively terminated. NRTIs should therefore represent the ideal antiviral agent. Unfortunately, HIV-1 inevitably develops resistance to these inhibitors, and this resistance correlates with mutations in RT. To date, three phenotypic mechanisms have been identified or proposed to account for HIV-1 RT resistance to NRTIs. These mechanisms include alterations of RT discrimination between NRTIs and the analogous dNTP (direct effects on NRTI binding and/or incorporation), alterations in RT-template/primer interactions, which may influence subsequent NRTI incorporation, and enhanced removal of the chain-terminating residue from the 3' end of the primer. These different resistance phenotypes seem to correlate with different sets of mutations in RT. This review discusses the relationship between HIV-1 drug resistance genotype and phenotype, in relation to our current knowledge of HIV-1 RT structure.

Polymerases:

Topics:

Status:

new topics/pols set partial results complete validated

Results:

No results available for this paper.

Entry validated by:

Log in to edit reference All References

Using Polbase tables:

Sorting:

Tables may be sorted by clicking on any of the column titles. A second click reverses the sort order. <Ctrl> + click on the column titles to sort by more than one column (e.g. family then name).

Filtering:

It is also possible to filter the table by typing into the search box above the table. This will instantly hide lines from the table that do not contain your search text.