Estimating the origin and evolution characteristics for Korean HIV type 1 subtype B using Bayesian phylogenetic analysis.

The majority of Korean human immunodeficiency virus type 1 (HIV-1) isolates are composed of the Korean clade B strain that is distinct from the subtype B prevalent in North America and Europe. However, it is still not clear how HIV-1 was introduced, transmitted, and evolved within the Korean population. To identify the evolutionary characteristics of Korean HIV-1, we estimate the molecular epidemic history of HIV-1 subtype B gp120 env in Korea in comparison with sequences isolated from other geographic locations. A Bayesian Markov chain Monte Carlo (MCMC) statistical inference was used to estimate the time of divergence of subtype B. The estimated time of divergence of subtype B and the distinct monophyletic Korean B cluster was estimated to be in the early and mid-1960s, respectively. Substitution rates were estimated at 7.3×10(-3) and 8.0×10(-3) substitutions per site per year for HIV-1 subtype B and Korean clade B, respectively. The demographic dynamics of two Korean data sets showed that the effective number of infections in Korea increased rapidly until the early 1980s, and then the rate only slowly increased until the mid-1990s when the population growth approached a steady-state. These results suggest that the growth rate of prevalent HIV-1 strains in Korea was lower than in other countries, suggesting that the evolution of HIV-1 Korean clade B was relatively slow. Furthermore, the limited transmission of HIV-1 within the Korean population likely led to the independent evolution of this virus to form the HIV-1 Korean clade B.

Broad neutralizing antibody response and genetic variation in HIV-1 env genes in Koreans with primary HIV-1 infections.

To determine the neutralization profiles induced by HIV-1 Korean clade B, which has a monophyletic lineage and relative limited genetic diversity, we investigated the ability of HIV variants to elicit neutralizing antibodies in the immune response to primary infection. We selected seven Korean drug-naïve subjects with an HIV-1 primary infection and did pseudovirion-based neutralization assays using env genes of Korean HIV origin. The neutralizing antibody responses to the Korean clade B showed broad reactivity to subtype B but a highly subtype-specific pattern. The lengths of the amino acid sequences and the PNGS numbers in the V1-V5 region were positively correlated with neutralization. These results imply that the genetic characteristics of HIV-1 env may affect neutralizing antibody responses in HIV-1-infected individuals. This is the first report describing the relationship between neutralizing antibody responses and HIV-1 genetic characteristics in Korean subjects. It can be useful for developing AIDS vaccines against HIV-1 subtype B strains.

Neutralizing Antibody Responses and Evolution of the Viral Envelope in the Course of HIV-1 Korean Clade B Infection.

OBJECTIVES: HIV is able to continuously adapt to and evade the evolving neutralizing antibody responses of the host. We investigated the ability of HIV variants to evade neutralizing antibodies in order to understand the distinct characteristics of HIV-1 Korean clade B. METHODS: Three drug-naive subjects were enrolled in this study who were infected with HIV-1 Korean clade B. Neutralizations were performed using autologous plasma and pseudovirion-based assays in order to analyze and compare changes in the env gene. RESULTS: In the early phase of infection, neutralizing activities against autologous virus variants gradually increased, which was followed by a decline in the humoral immune response against the subsequent viral escape variants. The amino acids lengths and number of potential N-linked glycosylation sites (PNGS) in HIV-1 env gene was positively correlated with neutralized antibody responses during the early stages of infection. CONCLUSION: This study suggests that change within the env domains over the course of infection influences reactivities to neutralized antibodies and may also have an impact on host immune responses. This is the first longitudinal study of HIV-1 humoral immunity that took place over the entire course of HIV-1 Korean clade B infection.

National survey of prevalent HIV strains: limited genetic variation of Korean HIV-1 clade B within the population of Korean men who have sex with men.

The evolution of HIV is the result of an explosive combination of factors-a high rate of mutation, replication dynamics, frequent recombination, and natural selection. To understand the evolution of the distinctive Korean HIV-1 B clade, we investigated the characteristics of the genetic variation of the HIV-1 subtype B env gene within the group of Korean men who have sex with men (MSM). From 1985 to 2005, 700 HIV-1-infected Koreans were sequenced at the V1 to V5 region of the HIV-1 env gene. In the phylogenetic analysis, 560 isolates were identified as HIV-1 subtype B, and 489 of the 560 isolates were HIV-1 Korean clade B. Based on epidemiologic investigation, 249 of 700 HIV-1-infected patients were HIV-1 subtype B-infected MSM. Interestingly, the proportion of the GPGS motif in MSM infected by Koreans was 1.6 times higher than in MSM infected by foreigners, and the genetic expansions of diversity and divergence for HIV-1 subtype B in Korean MSM were 2.1% and 2.5%, respectively. This was much lower than those observed in other countries. Therefore, our findings imply that the HIV strains in this group were closely related. This result may be helpful for understanding the evolution of the distinct HIV-1 Korean B clade.