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.