Signature pattern analysis for the full-length env gene of the earliest Korean subclade B of HIV-1: outbreak among Korean hemophiliacs

Abstract

The epidemiological link in the hypervariable env gene between viruses infecting HIV-positive hemophiliacs (HPs) and plasma donors was not studied. We determined full-length env gene sequences in 20 HPs, 3 plasma donors whose plasma was used for domestic clotting factor (DCF) production, and 54 local controls (LCs). Env genes from viruses in frozen stored sera obtained 1-3 years after diagnosis and from samples collected several years after infection were amplified via RT-PCR and subjected to direct sequencing. Phylogenetic analysis indicated that all sequences were subtype B, including 133 sequences from 77 cases (20 HPs, 3 plasma donors, and 54 LCs) belonging to the Korean subclade B (KSB) and 6 sequences from 5 cases that did not belong to the KSB. Env gene sequences from donors O and P and those of the 20 HPs comprised 2 subclusters within the KSB, although phylogenetic analysis did not support significant bootstrap values. In contrast, signature pattern analysis indicated signature nucleotides at 43 positions between the HPs and LCs (P < 0.05). In particular, specific signature nucleotides at 4 positions were fully conserved in the HPs, but not in the LCs (P < 0.0001). Furthermore, there were 26 signature residues within the KSB and were distinct from the worldwide consensus for subtype B. In conclusion, signature pattern analysis for the hypervariable env gene revealed an epidemiological link that the 20 HPs in this study had been infected with viruses from the DCF used for treatment, consistent with our previous finding.

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

“…This is the first study to compare several genes in an HIV-1 outbreak with transmission. We identified 12 signature amino acid residue patterns in the KSB Gag protein that are distinct from worldwide consensus B, and confirmed a previously postulated epidemiological link between the viruses that infected 20 HPs and two plasma donors, in contrast with those that infected local controls (LCs), as shown in previous studies [2,3,4,5].…”

“…Their plasma was used to manufacture clotting factor 9. The details have been described previously [2,3,4,5]. In total, 251 HIV-1-infected patients were diagnosed in Korea before 1992.…”

“…We have previously conducted a nationwide genetic analysis of HIV-1 with sera from individuals in the early stages of infection with HIV-1 (before 1994) with the aim of identifying the cause of an HIV-1 outbreak among hemophiliacs in Korea in 1990–1994. As a result of these molecular epidemiological studies, viruses from two plasma donors, who were paid to donate, were identified as the agents of infection of 20 HIV-1-infected hemophiliacs [1,2,3,4,5]. In these studies [1,2,3,4,5], we conducted in-depth analysis of the pol, vif, env , and nef genes in the Korean subclade of subtype B (KSB) [6,7], but the gag gene is yet to be studied in Korea.…”

“…KSB is presumed to have originated from strains in the USA through the founder effect [6,7], and the most recent common ancestor is estimated to have been active around 1984 [8]. The earliest case KSB HIV-1, was diagnosed in 1988 [2,3,4,5].…”

“…This study is the final in a series of genetic analyses of KSB, and provides a comprehensive nationwide analysis of the earliest-known gag sequences in Korea [2,3,4,5]. This is the first study to compare several genes in an HIV-1 outbreak with transmission.…”