Faculty Opinions recommendation of Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance.

ABSTRACT We have compared nucleotide substitutions and polymorphisms at codons known to confer drug resistance in subtype B strains of human immunodeficiency virus type 1 (HIV-1) with similar substitutions in viruses of other subtypes. Genotypic analysis was performed on viruses from untreated individuals. Nucleotide and amino acid diversity at resistance sites was compared with a consensus subtype B reference virus. Among patients with non-subtype B infections, polymorphisms relative to subtype B were observed at codon 10 in protease (PR). These included silent substitutions (CTC→CTT, CTA, TTA) and an amino acid mutation, L10I. Subtype A viruses possessed a V179I substitution in reverse transcriptase (RT). Subtype G viruses were identified by silent substitutions at codon 181 in RT (TAT→TAC). Similarly, subtype A/G viruses were identified by a substitution at position 67 in RT (GAC→GAT). Subtype C was distinguished by silent substitutions at codons 106 (GTA→GTG) and 219 (AAA→AAG) in RT and codon 48 (GGG→GGA) in PR. Variations relative to subtype B were seen at RT position 215 (ACC→ACT) for subtypes A and A/E. These substitutions and polymorphisms reflect different patterns of codon usage among viruses of different subtypes. However, the existence of different subtypes may only rarely affect patterns of drug resistance-associated mutations.

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Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population

Clinical Infectious Diseases ◽

10.1093/cid/ciy453 ◽

2018 ◽

Vol 68 (2) ◽

pp. 213-221 ◽

Cited By ~ 15

Author(s):

Soo-Yon Rhee ◽

Dana Clutter ◽

W Jeffrey Fessel ◽

Daniel Klein ◽

Sally Slome ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Molecular Epidemiology ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Immunodeficiency Virus ◽

Genetic Mechanisms ◽

Clinic Population

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Increased G→A Transition Frequencies Displayed by Primer Grip Mutants of Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Journal of Virology ◽

10.1128/jvi.78.2.1012-1019.2004 ◽

2004 ◽

Vol 78 (2) ◽

pp. 1012-1019 ◽

Cited By ~ 11

Author(s):

Clara E. Cases-González ◽

Luis Menéndez-Arias

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Target Sequence ◽

Strand Transfer ◽

Wild Type ◽

Reverse Transcriptases ◽

Immunodeficiency Virus ◽

Reported Data

ABSTRACT A genetic screen based on the blue-white β-galactosidase complementation assay designed to detect G→A mutations arising during RNA-dependent DNA synthesis was used to compare the fidelity of mutant human immunodeficiency virus type 1 reverse transcriptases (RTs) with the mutations M230L and M230I with the wild-type enzyme, in the presence of biased deoxynucleoside triphosphate (dNTP) pools. The mutant RTs with the M230L and M230I changes were found to be 20 to 70 times less faithful than the wild-type RT in the presence of low [dCTP]/[dTTP] ratios but showed similar fidelity in assays carried out with equimolar concentrations of each nucleotide. Biased dNTP pools led to short tandem repeat deletions in the target sequence, which were also detectable with the assay. However, deletion frequencies were similar for all of the RTs tested. The reported data suggest that RT pausing due to the low dNTP levels available in the RT reaction mixture facilitates strand transfer, in a process that is not necessarily mediated by nucleotide misinsertion.

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