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Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility
C Apetrei1, D Descamps, G Collin
1Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, Paris, France.
Abstract:
We sequenced and phylogenetically analyzed the reverse transcriptase (RT) regions of the pol genes of 14 human immunodeficiency virus type 1 (HIV-1) isolates from Romanian patients, which were classified as subtype F on the basis of env gene structure. The RT sequences showed that the strains clustered phylogenetically and were equidistant from other HIV-1 subtypes as shown by the neighbor-joining and maximum-likelihood methods, allowing us to define HIV-1 subtype F according to the pol classification. The subtype F RT sequences differed from reported group M RT sequences by 10.94% (for nucleotides) and 7.6% (for amino acids). Phenotypic analysis of subtype F susceptibility to three classes of antiretroviral compounds showed an increase in the 50% inhibitory concentration of the tetrahydroimidazo[4,5,1-jk] [1,4]-benzodiazepin-2-(1H)-one and -thione (TIBO) derivate R82913 for one strain which was naturally resistant to this compound. This first report of subtype F pol sequences confirms the perfect correlation between the phylogenetic positions determined by env and pol analyses and suggests that virus variability might influence the efficacy of antiretroviral treatments. This finding warrants a global evaluation of the phenotypic and genotypic susceptibility of HIV-1 subtypes to antiretroviral drugs.
Insights
This study defines human immunodeficiency virus type 1 (HIV-1) subtype F using pol gene sequencing from Romanian patients. Findings suggest HIV-1 variability may impact antiretroviral treatment efficacy, necessitating broader drug susceptibility evaluations.
Area of Science:
- Virology
- Genetics
- Molecular Biology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) exhibits significant genetic diversity, with various subtypes impacting disease progression and treatment.
- Previous classification of Romanian HIV-1 isolates relied on env gene structure, necessitating confirmation through other genetic regions.
Purpose of the Study:
- To phylogenetically analyze the reverse transcriptase (RT) regions of the pol genes from 14 Romanian HIV-1 isolates.
- To confirm the classification of these isolates as HIV-1 subtype F based on pol gene sequences.
- To investigate the phenotypic susceptibility of subtype F to antiretroviral compounds.
Main Methods:
- Sequencing of the RT regions of the pol genes from 14 HIV-1 isolates.
- Phylogenetic analysis using neighbor-joining and maximum-likelihood methods.
- Phenotypic susceptibility testing against antiretroviral compounds, including TIBO derivative R82913.
Main Results:
- The Romanian HIV-1 strains clustered phylogenetically as subtype F based on pol gene analysis, correlating with env gene classification.
- Subtype F RT sequences showed significant divergence from Group M sequences (10.94% nucleotide, 7.6% amino acid).
- One strain exhibited natural resistance to R82913, indicating potential variability in drug susceptibility within subtype F.
Conclusions:
- This study provides the first report of HIV-1 subtype F pol sequences, confirming its distinct phylogenetic position.
- The findings highlight a strong correlation between env and pol gene phylogenetic analyses for HIV-1 classification.
- Virus genetic variability, as seen in subtype F, may influence antiretroviral treatment efficacy, underscoring the need for global evaluation of drug susceptibility across HIV-1 subtypes.