Evidence map›Paper›PMID 14512562›Full record

ArticleJournal of virology2003

Mutations in the 5' end of the human immunodeficiency virus type 1 polypurine tract affect RNase H cleavage specificity and virus titer.

Mary Jane McWilliams, John G Julias, Stefan G Sarafianos, W Gregory Alvord, Edward Arnold, Stephen H Hughes

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.0field-weighted citation impact, top 28% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Mary Jane McWilliamsHIV-Drug Resistance Program, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, Maryland 21702-1201, USA.
John G Julias
Stefan G Sarafianos
W Gregory Alvord
Edward Arnold
Stephen H Hughes
CNR de la Résistance aux Antibiotiques · FRRutgers, The State University of New Jersey · USData Management Services (United States) · USNational Institutes of Health · US

Funding

STRUCTURES OF HIV REVERSE TRANSCRIPTASE WITH SUBSTRATESR37AI027690 · NIAID · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI ARNOLD, EDWARD · 1999 to 2018
$14.4M
STRUCTURES OF HIV REVERSE TRANSCRIPTASE WITH SUBSTRATESR01AI027690 · NIAID · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI EDWARD ARNOLD · 1989 to 2026
$4.3M
Retroviral Replication and Vector DesignZ01BC010482 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUGHES, STEPHEN H · 2003 to 2008
$2.3M
HIV REVERSE TRANSCRIPTASE WITH RNA/DNA DUPLEXESF32AI009578 · NIAID · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI SARAFIANOS, STEFANOS · 1996 to 1998
–
NIAID NIH HHS AI 09578NIAID NIH HHS AI 27690NIAID NIH HHS F32 AI009578NIAID NIH HHS R01 AI027690NIAID NIH HHS R37 AI027690NIGMS NIH HHS GM55609
6 · The paper itself

Abstract

The RNase H activity of retroviral reverse transcriptases (RTs) degrades viral genomic RNA after it has been copied into DNA, removes the tRNA used to initiate negative-strand DNA synthesis, and generates and removes the polypurine tract (PPT) primer used to initiate positive-strand DNA synthesis. The cleavages that remove the tRNA and that generate and remove the PPT primer must be specific to generate linear viral DNAs with ends that are appropriate for integration into the host cell genome. The crystal structure of human immunodeficiency virus type 1 (HIV-1) RT in a complex with an RNA/DNA duplex derived from the PPT revealed that the 5' end of the PPT deviates from traditional Watson-Crick base pairing. This unusual structure may play a role in the proper recognition of the PPT by HIV-1 RT. We made substitution mutations in the 5' end of the PPT and determined their effects on virus titer. The results indicated that single and double mutations in the 5' end of the PPT had modest effects on virus replication in a single-cycle assay. More complex mutations had stronger effects on virus titer. Analysis of the two-long-terminal-repeat circle junctions derived from infecting cells with the mutant viruses indicated that the mutations affected RNase H activity, resulting in the retention of PPT sequences on viral DNA. The mutants tested preferentially retained specific segments of the PPT, suggesting an effect on cleavage specificity. These results suggest that structural features of the PPT are important for its recognition and cleavage in vivo.

Indexed as

Base SequenceCell LineDNA, ViralHIV-1HIV Long Terminal RepeatHIV Reverse TranscriptaseHumansMolecular Sequence DataMutationRibonuclease HRNAVirus ReplicationDNA, ViralHIV Reverse TranscriptaseRibonuclease HRNARNA primers

Identifiers

PMID14512562
PMCPMC224987
OpenAlexW2146311111

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.