ArticleAIDS (London, England)2010
N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations.
Article in AIDS (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Frequent emergence of N348I in HIV-1 subtype C reverse transcriptase with failure of initial therapy reduces susceptibility to reverse-transcriptase inhibitors.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2012Trial
- Zidovudine (AZT) monotherapy selects for the A360V mutation in the connection domain of HIV-1 reverse transcriptase.PloS one · 2012Trial
- The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.Journal of virology · 2014Article
- Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine.Antiviral research · 2014Article
- Article
- N348I in HIV-1 reverse transcriptase counteracts the synergy between zidovudine and nevirapine.Journal of acquired immune deficiency syndromes (1999) · 2012Article
- HIV-1 reverse transcriptase (RT) polymorphism 172K suppresses the effect of clinically relevant drug resistance mutations to both nucleoside and non-nucleoside RT inhibitors.The Journal of biological chemistry · 2012Article
- Article
- A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation.Journal of virology · 2012Article
- Subunit-specific mutational analysis of residue N348 in HIV-1 reverse transcriptase.Retrovirology · 2011Article
- Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations.The Journal of antimicrobial chemotherapy · 2011Article
- The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine.The Journal of biological chemistry · 2010Article
- Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure.Antimicrobial agents and chemotherapy · 2010Article
- Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment.European journal of medical research · 2010Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveSeveral nonnucleoside (e.g. Y181C) and nucleoside (e.g. L74V and M184V) resistance mutations in HIV-1 reverse transcriptase are antagonistic toward thymidine analogue mutations (TAMs) that confer zidovudine (ZDV) resistance. The N348I mutation in the connection domain of reverse transcriptase also confers ZDV resistance; however, the mechanisms involved are different from TAMs. In this study, we examined whether N348I compensates for the antagonism of the TAM K70R by Y181C, L74V and M184V. DESIGN AND
methodsThe ZDV monophosphate and ribonuclease H activities of recombinant-purified HIV-1 reverse transcriptase-containing combinations of K70R, N348I and Y181C, L74V or M184V were assessed using standard biochemical and antiviral assays.
resultsAs expected, the introduction of the Y181C, L74V or M184V mutations into K70R HIV-1 reverse transcriptase significantly diminished the ATP-mediated ZDV monophosphate excision activity of the enzyme. However, the N348I mutation compensated for this antagonism on RNA/DNA template/primers by significantly decreasing the frequency of secondary ribonuclease H cleavages that reduce the overall efficiency of the excision reaction.
conclusionThe acquisition of N348I in HIV-1 reverse transcriptase - which can occur early in therapy, oftentimes before TAMs - may provide a simple genetic pathway that allows the virus to select both TAMs and mutations that are antagonistic toward TAMs.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.