Variabilidad genómica del virus de la Inmunodeficiencia Humana tipo I en individuos con conductas de alto riesgo y su impacto sobre la capacidad replicativa viral in vitro
The genetic characterization of the Human Immunodeficiency Virus Type 1 (HIV-1)\nepidemic in Argentina showed that subtype B is the most prevalent in men who have\nsex with men while BF recombinant forms are most prevalent among heterosexuals\nand intravenous drug users. Thus, patients with multiple...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2014
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_781 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_781.dir/781.PDF |
| Aporte de: |
| Sumario: | The genetic characterization of the Human Immunodeficiency Virus Type 1 (HIV-1)\nepidemic in Argentina showed that subtype B is the most prevalent in men who have\nsex with men while BF recombinant forms are most prevalent among heterosexuals\nand intravenous drug users. Thus, patients with multiple epidemiological risks may be\nexposed to both. The gag/pol genomic region plays a fundamental role during the viral\nlife cycle and it has been shown that recombination is a common feature in this region,\nwhich may affect the viral replication capacity (RC) of the recombinant virus. Herein we\nanalyzed the presence of HIV dual infections in individuals with high probability of reinfection\nand we evaluated the impact of intersubtype recombination in the gag/pol\nregion on viral RC and relative RC.\nThree dual infections were detected, two corresponded to individuals co-infected with\nsubtype B and BF recombinant variants, and one was co-infected with two BF\nrecombinant variants. Prolonged infection with a stable clinical condition was observed\nin the three individuals. Resistance mutation patterns were different between the\npredominant and the minority strains. The analysis of Gag and Gagpol sequences\nshowed, for the first time in Argentina, a high natural polymorphism in subtype F and\nBF recombinants variants in comparison with subtype B isolates. The in vitro evaluation\nof RC of two BF recombinant forms revealed that the recombination in the Gag-\nProtease region was associated with a decrease in viral particles production when\ncompared to the B variant. Furthermore, when challenged with subtype B in a dual\ncompetition assay, the BF variants were less efficient than subtype B, reaching a lower\nfrequency in the viral population in a short period of time.\nIn conclusion, our results show that HIV dual infection can occur with closely related\nsubtypes, and even with different variants of the same recombinant form. The\ncomparison of the primary structure of gag/pol sequences between F1 subtype, BF\nrecombinants variants and B subtype isolates, showed that non-B HIV-1 strain were\nhighly polymorphic in positions related with PI exposure and/or resistance. In addition,\nwe describe for the first time the in vitro dynamics of gag-protease-associated RC of\nHIV-1 intersubtype variants, compared with that of subtype B. This study provides\nevidence that intersubtype recombination in this region might alter viral RC generating\nvariants with reduce fitness.\n |
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