Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years.

Young-Keol Cho,Brian T Foley,Jung-Eun Kim

doi:10.3390/v13050806

Young-Keol Cho, Brian T Foley + Show 1 more

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https://doi.org/10.3390/v13050806

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Abstract

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

Highlights

We previously conducted a nationwide genetic analysis of HIV-1 using sera from individuals in the early stages of HIV-1 infection to identify the cause of the HIV-1 outbreak among patients with hemophilia in Korea in 1990–1994
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
We found that patient BGO, who was diagnosed in July 1988, was the first patient infected with KSB (MT559045)

Summary

Introduction

We previously conducted a nationwide genetic analysis of HIV-1 using sera from individuals in the early stages of HIV-1 infection (before 1994) to identify the cause of the HIV-1 outbreak among patients with hemophilia in Korea in 1990–1994. 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 genetic analysis, but a few genes are yet to be explored. The most recent common ancestor virus is estimated to have been active around 1984 [14]; the earliest infection case was diagnosed in 1988 [2,3,4,5,6]

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