Human immunodeficiency virus type 1 subtype F reverse transcriptase sequence and drug susceptibility

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.

FIG. 1

Alignment of the deduced amino acid sequences of HIV-1 subtype F RT and the consensus (Cons) sequences of HIV-1 group M and group O strains. Strains RO-BCI17 to RO-BCI23 were isolated from HIV-1-infected adults. ∗, established following the analysis of the pol sequences originating from 11 Zimbabwean seroconverters (32). ∗∗, naturally resistant to TIBO derivate.

FIG. 2

Phylogenetic analysis comparing the RT regions of HIV-1 pol genes from different strains. Tree topology was inferred by the neighbor-joining method. The tree was based on an alignment of nucleotides from which columns containing gaps have been deleted (597 nucleotides). The tree was rooted with HIV-1 group O sequences. The numbers given at the branch points are the 50% threshold majority consensus values for 100 bootstrap replicates. Vertical distances are given for clarity. The cluster of sequences from nosocomially infected children (∗) had already been observed by analyzing the env gene (1). Strain RO-BCI13 (∗∗) was isolated from a vertically infected child. Strains RO-BCI17, RO-BCI18, RO-BCI19, RO-BCI20, and RO-BCI23 were isolated from HIV-1-infected adults.