Caracterização molecular de recombinantes intersubtipos do vírus da imunodeficiência humana tipo 1(HIV-1) em pacientes provenientes da epidemia do estado de São Paulo. / Molecular characterization of recombinant intersubtipos of human immunodeficiency virus type 1 (HIV-1) in patients from the epidemic in the state of Sao Paulo, Brazil.

Fernando Mario Rodrigues Marques

The extensive HIV-1 genetic diversity has several implications on the viral adaptive and evolutionary capabilities. This diversity is due to intensive mutational rates derived from error-prone activity of viral reverse transcriptase and RNA genomic instability, generating a highly diverse and heterogeneous viral population named quasispecies. However, even this intensive genetic variability passes through drastic genetic variants decrease events that decreases the numbers of viruses less adapted to the host pressures, bringing about a constant oscillation of the viral genetic characteristics within a population. Besides mutational events, there is the possibility that intra and intersubtype genomic recombination events can favor the generation of genetic diversity, making viruses capable of overcoming selective pressures.. The proposal of the study was to analyze molecular characteristics of HIV-1 intersubtype recombinants from São Paulo State epidemics, Brazil, in order to evaluate if the recombination events and recombination-derived population genetic fluctuation can influence the evolution of the infection in in vivo conditions. To do so, eleven newly-infected individuals with intersubtype recombinant viruses (based on full-length genome sequencing by bulk PCR) were selected and had their PBMCs samples collected each three months, during a one year and three months period, so that a prospective proviral load, viral load and CD4+ T cells count follow-up was performed. The analysis of the evolution patterns on laboratory parameters showed a significant variation between individuals, without any substantial difference between recombinant infection and pure clade infection. Moreover, proviral DNA samples relative to each three-month period (called visit) were amplified and had their protease-region restriction patterns mapped, showing that from 10 supposed recombinants 20% were, in fact, cases of double infections by pure B and F1 clades, these data being consistent with the double infections prevalence sub-estimation in São Paulo State. Following that, 1,2 kb pol fragments (including protease and part of reverse transcriptase) of each visit from individuals infected with both intersubtype recombinants and double infections were cloned, selecting ten clones from each condition for fragment sequencing and recombination breakpoints mapping. We observed that the visit one (V1) viral recombination breakpoints on the referred fragment were not seen on the further visits clones, and most of the 3 end breakpoints persisted on the viral population through the observation period. Furthermore, the viral genetic diversity tended to be bigger on patients where there were recombination events.

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