RESUMEN
Molecular phylogenetic studies of the HIV-1 isolated from Koreans have suggested the presence of the so-called "Korean clade", which can be defined as a cluster free of foreign isolates. The Korean clade accounts for more than 60% of Korean isolates and exerts characteristic amino acid sequences. Thus, it is merited to estimate when this Korean clade first emerged in order to understand the evolutionary pattern of the Korean clade. We analyzed and reconstructed the most recent common ancestor (MRCA) sequences from nef (n=229) and vif (n=179) Korean clade sequences. Linear regression analyses of sequence divergence estimates were plotted against sampling years to infer the year in which there was zero divergence from the MRCA sequences. MRCA sequences suggested the Korean clade was first emerged around 1984, before the first detection of HIV-1 in Korea in 1985. Further studies on synonymous and nonsynonymous substitution rates suggested positive selection event for the Korean clade, while other subtype B had undergone negative to neutral evolution.
Asunto(s)
Evolución Molecular , Infecciones por VIH/virología , VIH-1/genética , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/genética , ADN Viral/análisis , Flujo Genético , Infecciones por VIH/genética , Humanos , Corea (Geográfico) , Análisis de Regresión , Análisis de Secuencia de ADN , Factores de TiempoRESUMEN
Phylogenetic studies of the HIV-1 gene sequences isolated from Korean patients have suggested that most of Korean isolates belong to the subtype B strain. This study aims to characterize the Korean clade by molecular phylogenetic analysis using all of the Korean nef gene sequences registered in the NCBI GenBank (N=422), in addition to 41 reference strains and 94 foreign isolates. Through phylogenetic analyses, we verified that most of the Korean isolates belonged to the subtype B, where 78.8% are clustered exclusively of foreign isolates. This cluster has been named the Korean clade subtype B (KCB) in order to distinguish it from other subtype B clusters. Genetic distance analysis suggested that the KCB cluster was more homogeneous and clearly distinctive from the non-Korean clade subtype B (NKCB). Comparison of consensus amino acid sequences from KCB and NKCB revealed that characteristic KCB signature amino acid patterns composed of 11 amino acid residues, whose frequencies in the KCB were significantly higher than in the NKCB. The KCB signature amino acid residues were critical in identifying KCB from NKCB, since substitution of the NKCB sequences with KCB signature amino acids relocated them to the Koran clade, and vice versa.
Asunto(s)
Genes nef , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Codón sin Sentido , Secuencia de Consenso , VIH-1/aislamiento & purificación , Humanos , Corea (Geográfico) , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Nucleotide and amino acid substitution pattern in vif gene of the Korean clade of HIV-1 isolated from Koreans were analyzed using consensus sequences. At nucleotide level, transition/transversion substitution ratio was 1.88, and nonsynonymous/synonymous substitution ratio was 2.67, suggesting a divergent evolution in the Korean clade. At amino acid level, there were 17 substitutions and G-->E substitution at position 37 may be responsible for change in predicted secondary structure.
Asunto(s)
Evolución Molecular , Genes vif , Infecciones por VIH/virología , VIH-1/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Pueblo Asiatico , Secuencia de Bases , Secuencia de Consenso , Productos del Gen vif/química , Productos del Gen vif/genética , VIH-1/clasificación , Humanos , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Alineación de Secuencia , Productos del Gen vif del Virus de la Inmunodeficiencia HumanaRESUMEN
Phylogenetic studies of nef, pol, and env gene sequences of HIV-1 isolated from Koreans suggested the presence of a Korean clade in which Korean sequences are clustered to the exclusion of foreign sequences. We attempted to identify and characterize the Korean clade using all vif gene sequences isolated from Koreans registered in the NCBI GenBank database (n = 233). Most (77 %) of the Korean isolates belonged to the Korean clade as a large subcluster in subtype B, designated the Korean clade subtype B (KCB). KCB sequences were relatively homogenous compared to Korean subtype B sequences that did not belong to the KCB (non-Korean clade subtype B; NKCB). Comparison of amino acid frequencies of KCB and NKCB sequences revealed several positions where the amino acid frequencies were significantly different. These amino acid residues were critical in separating KCB from NKCB or from foreign sequences, since substitution of these amino acids in KCB with the NKCB amino acids relocated the KCB sequences to NKCB, and vice versa. Further analyses of KCB will help us to understand the origin and evolutionary history of KCB.
