Biomaterial Database

The effect of increased processivity on overall fidelity of human immunodeficiency virus type 1 reverse transcriptase. 2001

L F Rezende, and Y Kew, and V R Prasad

Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, N.Y. 10461, USA.

We previously reported that two insertions of 15 amino acids in the beta3-beta4 hairpin loop of fingers subdomain of HIV-1(NL4-3) RT confer an increased polymerase processivity. The processivity of human immunodeficiency virus (HIV) reverse transcriptase (RT) is thought to influence the fidelity of HIV-1 RT, which tends to create errors at template sites with high termination probability. Employing the two insertion variants of HIV-1 RT (FE20 and FE103), we examined the relationship between processivity, overall fidelity and error specificity. Although the overall mutation rate was unaffected by increased processivity, one of the mutants, FE103, generated significantly fewer frameshift errors. The other mutant, FE20, generated errors at hotspots not previously observed for HIV-1 RT. Our results indicate that an increase in the polymerase processivity of HIV-1 RT does not necessarily result in a decreased mutation rate and confirm that changes in processivity alter the sequence context in which the errors are made. Furthermore, our results also reveal that the mutation frequency obtained via in vitro gap-filling reactions with wild-type HIV-1(NL4-3) RT is only 2-fold higher than that obtained via a single cycle infection assay using the same, wild-type HIV-1(NL4-3) RT sequence as part of the helper pol function [Mansky and Temin: J Virol 69:5087-5094;1995].

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D004252	DNA Mutational Analysis	Biochemical identification of mutational changes in a nucleotide sequence.	Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D004279	DNA, Viral	Deoxyribonucleic acid that makes up the genetic material of viruses.	Viral DNA
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D013698	Templates, Genetic	Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.	Genetic Template,Genetic Templates,Template, Genetic
D015497	HIV-1	The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.	Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D016296	Mutagenesis	Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.	Mutageneses
D016368	Frameshift Mutation	A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.	Mutation, Frameshift,Frame Shift Mutation,Out-of-Frame Deletion,Out-of-Frame Insertion,Out-of-Frame Mutation,Deletion, Out-of-Frame,Deletions, Out-of-Frame,Frame Shift Mutations,Frameshift Mutations,Insertion, Out-of-Frame,Insertions, Out-of-Frame,Mutation, Frame Shift,Mutation, Out-of-Frame,Mutations, Frame Shift,Mutations, Frameshift,Mutations, Out-of-Frame,Out of Frame Deletion,Out of Frame Insertion,Out of Frame Mutation,Out-of-Frame Deletions,Out-of-Frame Insertions,Out-of-Frame Mutations