Phylogenetic Analysis of the EarliestnefGene from Hemophiliacs and Local Controls in Korea

Abstract

Twenty hemophiliacs (HPs) were found to have human immunodeficiency virus type-1 (HIV-1) 1–2 years after exposure to Factor IX manufactured in Korea in late 1989. Plasma samples collected from donors O and P during their pre-seroconversion acute infection stage were used to manufacture clotting factors, including Factor IX, to treat these patients. To assess whether a genetic relationship exists between the viruses infecting HIV-1-positive HPs and those infecting plasma donors, we evaluated the nef sequences in 216 individuals. Frozen-stored serum samples obtained 1–3 years after the diagnosis of HIV-1 in the 20 HPs were used for amplification of the nef gene by reverse transcriptase–polymerase chain reaction, and amplicons were subjected to direct sequencing. Phylogenetic analysis revealed that the nef sequences from 143 of the samples belonged to the Korean subclade of HIV-1 subtype B (KSB). Sequences of the nef gene from donors O and P and the 20 HPs comprised two subclusters within KSB together with several local control (LC) sequences. In addition, signature pattern analysis revealed the presence of conserved nucleotides at eight positions in donors O and P compared with LCs (p<0.01). These nationwide and comprehensive nef data support the previous conclusion that HPs were infected with HIV-1 from the clotting factor, although the stringency of nef is weaker than for the pol and vif genes.

Long‐term follow up of HIV‐1‐infected Korean haemophiliacs, after infection from a common source of virus

“…The patients had been primarily treated with imported clotting factors prior to the use of the domestic clotting factor. To date, four of these HPs have died . We reviewed medical records.…”

“…During the time of our present study, four HPs had already died . The remaining 16 HPs have been treated with HAART and Korean red ginseng (KRG).…”

Molecular Epidemiology of Human Immunodeficiency Virus

“…Phylogenetic analyses were also utilized for epidemiologic evaluation of HIV-infected Korean hemophilia patients [6869], and investigation of HIV-1-transmitted drug resistance (TDR) in Korea [6468707172]. Studies on TDR revealed that the drug resistance mutation was not common among treatment-naïve HIV-infected individuals in Korea, and there was little evidence to suggest that TDR in Korea is related to the clonal spread of drug-resistant strains.…”

Phylogenetic Analysis of Near Full-Length HIV Type 1 Genomic Sequences from 21 Korean Individuals

“…Among various subtypes and CRFs in Korea, domestically infected Korean individuals are mainly infected with the Korean subclade of subtype B (KSB) at the level of the env, nef, pol, and vif genes. [1][2][3][4][5][6] KSB sequences were first detected in homosexual Korean HIV-1 patients in 1988. 1 Our previous studies show that these KSB sequences represent a subclade of the globally represented subtype B, indicating a founder effect.…”

“…This finding is consistent with our previous studies on vif, pol, and nef genes. 1,5,6 TATA box sequences in both LTR were classified as TATAA for subtype B and almost all other subtypes, and CRFs. However, TAAAA instead of TATAA was identified in CRF01_AE, some cpx strains, and CPZ.US.85.US_Marilyn.…”