RESUMO
Twenty hemophiliacs were infected with Korean subclade B (KSB) of HIV-1 from two cash-paid plasma donors in Korea in 1990. Our previous studies revealed that Korean red ginseng (KRG) intake increases the frequency of gross deletion in the nef gene (gDeltanef). We investigated whether KRG and highly active antiretroviral therapy (HAART) affected the frequency of gDeltanef in the 20 hemophiliacs who share common characteristics of the HIV-1 source, mode of transmission, and infection time. Over a 10-year period, we obtained 522 nef amplicons by nested PCR using 172 samples of peripheral blood mononuclear cells. Of the 522 nef amplicons, 69 (13.2%) were gDeltanef. Despite a 2-fold higher monthly dose of KRG, the frequency of gDeltanef detection (3.2%) was significantly reduced during HAART compared with that prior to HAART (20.6%) (p < 0.001). gDeltanef was detected significantly more in patients treated with a monthly KRG intake of more than 60 g (26.8%) than in patients treated with a monthly KRG intake of less than 60 g (10.5%) (p < 0.05). These finding suggest that the frequency of gDeltanef is dependent on the amount of KRG intake, although further study is needed. These data might provide a new perspective on the pathogenesis of HIV-1.
Assuntos
Terapia Antirretroviral de Alta Atividade , Genes nef/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Hemofilia A , Panax , Deleção de Sequência , Adolescente , Adulto , Criança , Pré-Escolar , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Humanos , Coreia (Geográfico) , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Análise de Sequência de DNA , Deleção de Sequência/efeitos dos fármacos , Adulto Jovem , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genéticaRESUMO
A triplex-forming oligonucleotide (TFO) complementary to the polypurine-polypyrimidine region of the nef gene of the Human Immunodeficiency Virus (HIV) was labeled with 125I at the C5 position of a single deoxycytosine residue. Labeled TFO was incubated with a plasmid containing a fragment of the nef gene. Decay of 125I was found to cause double-strand breaks (DSB) within the nef gene upon triplex formation in a sequence specific manner. No DSB were detected after incubation at ionic conditions preventing triplex formation or when TFO was labeled with 32P instead of 125I. Mapping DSB sites with single base resolution showed that they are distributed within 10 bp of a maximum located exactly opposite the position of the [125I] IdC in the TFO. We estimate that on average the amount of DSB produced per decay is close to one.