RESUMEN
This work is aimed at assessing the presence of positive selection and/or shifts of the evolutionary rate in a fast-expanding HIV-1 subtype F1 transmission cluster affecting men who have sex with men in Spain. We applied Bayesian coalescent phylogenetics and selection analyses to 23 full-coding region sequences from patients belonging to that cluster, along with other 19â¯F1 epidemiologically-unrelated sequences. A shift in the overall evolutionary rate of the virus, explained by positively selected sites in the cluster, was detected. We also found one substitution in Nef (H89F) that was specific to the cluster and experienced positive selection. These results suggest that fast transmission could have been facilitated by some inherent genetic properties of this HIV-1 variant.
Asunto(s)
Evolución Molecular , Genoma Viral , Genómica , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/genética , Antígenos Virales/inmunología , Bases de Datos Genéticas , Epítopos de Linfocito T/inmunología , Genómica/métodos , Infecciones por VIH/inmunología , Infecciones por VIH/transmisión , VIH-1/inmunología , Humanos , Filogenia , Recombinación Genética , Selección Genética , Factores Sexuales , España/epidemiologíaRESUMEN
Primary resistance mutations to fusion inhibitors and polymorphisms in gp41 sequences of non-B subtypes and recombinant HIV-1 isolates were analysed. L91H to RPR103611 was detected in one DGpol/Denv/Dgp41 recombinant; L9F and K144R, rarely reported previously, were frequent in the B region of CRF14_BG recombinants. V194I and V318A, not described in the G subtype, were detected in the G region of BG recombinants and in G subtype viruses that also show the rare mutations T115L, M118V and K90R.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Proteína gp41 de Envoltorio del VIH/genética , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/genética , Mutación/genética , Enfuvirtida , Proteína gp41 de Envoltorio del VIH/uso terapéutico , Humanos , Masculino , Fragmentos de Péptidos/uso terapéutico , Polimorfismo GenéticoRESUMEN
OBJECTIVES: To examine HIV-1 genetic diversity in St. Petersburg. METHODS: Partial HIV-1 pol sequences from 102 plasma samples collected in 2006 were analyzed with a Bayesian phylogeny inference method. RESULTS: Subtype A, former Soviet Union (FSU) variant (AFSU), was the predominant clade (89.3%); other clades were subtypes B (9.7%) and F1 (1%). AFSU was predominant both among injecting drug users (98.2%) and heterosexually infected individuals (91.4%), whereas subtype B was more prevalent among homosexual men (75%). Within the AFSU variant, most sequences (93.5%) branched within 1 of 4 strongly supported subclusters. The largest comprised 63% AFSU viruses and was uncommon outside St Petersburg. A second subcluster (17.4% AFSU viruses) corresponds to the variant with the V77I substitution in protease, which is widely circulating in different FSU countries. Two minor subclusters comprised 8.7% and 6.5% AFSU viruses, respectively. There was no correlation between risk exposure and AFSU subclusters. Six of 8 subtype B sequences, 4 of them from homosexual men, grouped in a monophyletic subcluster. CONCLUSIONS: The results of this study show a great predominance of AFSU viruses in St Petersburg and point to a few phylogenetically identifiable introductions as the origin of most current HIV-1 AFSU infections in the city.