Genetic Analysis of the Full-Length gag Gene from the Earliest Korean Subclade B of HIV-1: An Outbreak among Korean Hemophiliacs

Abstract

We determined the earliest full-length HIV-1 gag gene sequences in 110 patients with HIV-1, including 20 hemophiliacs (HPs) and 90 local controls (LCs). The gag gene from stored sera was amplified using RT-PCR, and was subjected to direct sequencing. Phylogenetic analysis indicated that 94 and 16 sequences belonged to the Korean subclade of HIV-1 subtype B (KSB) and subtype B, respectively. A total of 12 signature pattern amino acids were found within the KSB, distinct from the worldwide consensus of subtype B. Within the KSB, the gag gene sequences from donors O and P and those from the 20 HPs comprised two subclusters. In particular, sequences from donor O strongly clustered with those of eight HPs. Moreover, signature pattern analysis indicated that 14 signature nucleotides were shared between the HPs and LCs within KSB (p < 0.01). Among the 14 nucleotides, positions 9 and 5 belonged to clusters O and P, respectively. In conclusion, signature pattern analysis for the gag gene revealed 12 signature pattern residues within the KSB and also confirmed the previous conclusion that the 20 HPs were infected with viruses due to incompletely inactivated clotting factor IX. This study is the first genetic analysis of the HIV-1 gag gene in Korea.

The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution

“…The clinical characteristics of all patients were described in previous studies [ [2] , [3] , [4] , [5] , 19 ]. They all were infected with KSB from Plasma Donors O and P [ [2] , [3] , [4] , [5] , 19 ], and the earliest vif genes from Plasma Donors O and P were all wild-type (WT) ones [ 3 ]. In addition, we had obtained vif - vpr genes in the two plasma donors.…”

“…The twenty patients with hemophilia (HP), identified in this study as HP 1–HP 20, were diagnosed with HIV-1 infection between 1990 and 1994 ( Table S1 ) [ [2] , [3] , [4] , [5] , 19 ]. They had been treated primarily with imported clotting factors before the start of local domestic clotting factor production .…”

“…It is presumed that the Korean subclade of human immunodeficiency virus type 1 (HIV-1) subtype B (KSB) was introduced to Korea by the founder effect in the mid-1980s [ 1 , 2 ]. During late 1989 to early 1990, 20 hemophiliacs (HPs) were diagnosed with KSB infection 1–2 years after exposure to domestic clotting factor IX manufactured using plasma from two cash-paid plasma donors in Korea [ [2] , [3] , [4] ]. They all were infected with a single source of HIV-1 [ 3 , 4 ].…”

Sequence Length of HIV-1 Subtype B Increases Over Time: Analyzing a Cohort of Patients with Hemophilia Over 30 Years

“…We previously conducted a nationwide genetic analysis of HIV-1 with sera from individuals in the early stages of HIV-1 infection (before 1994) to identify the cause of an HIV-1 outbreak among patients with hemophilia in Korea in 1990-1994. These molecular epidemiological studies revealed that viruses from two cash-paid plasma donors were incompletely inactivated in the process of manufacturing clotting factor IX and were identified as the agents of infection among 20 HIV-1-infected patients with hemophilia and HIV-1 infection [1][2][3][4][5][6]. The viruses in 8 and 12 patients with hemophilia infected with the Korean subclade of HIV-1 subtype B (KSB) originated from plasma donors O and P, respectively.…”

“…The viruses in 8 and 12 patients with hemophilia infected with the Korean subclade of HIV-1 subtype B (KSB) originated from plasma donors O and P, respectively. In these studies [1][2][3][4][5][6][7], we conducted an in-depth analysis by genes, but a few genes are yet to be studied. The sequence length significantly affects the extent of clustering in a phylogenetic tree [8][9].…”