Analysis of evolutionary rate of HIV-1 subtype B using blood donor samples in Japan
There are few reports on HIV-1 intra-host evolutionary rate in asymptomatic treatment-naïve patients. Here, the HIV-1 intra-host evolutionary rate was estimated based on HIV-1 RNA sequences from plasma samples of blood donors in Japan. Blood donors were assumed to have received no treatment for and have no symptoms of HIV-1 infection because they were healthy, and declared no risky behaviors of HIV-1 infection on a self-reported questionnaire or interview followed by donation. HIV-1 RNA was obtained from 85 plasma samples from 36 blood donors who donated blood multiple times and were HIV-1-positive. The C2V3C3 region which encodes for a part of the envelope protein, and the V3 loop in the C2V3C3 region were analyzed by RT-PCR and direct sequencing, and the sequences were compared. The nucleotide substitution rate was calculated by linear regression. All HIV-1 samples analyzed were classified as subtype B. The mean nucleotide substitution rate in C2V3C3 was calculated to be 6.2 × 10−3–1.8 × 10−2/site/year (V3: 4.5 × 10−3–2.3 × 10−2/site/year). The mean non-synonymous substitution rate in C2V3C3 was calculated to be 5.2 × 10−3–1.7 × 10−2/site/year (V3: 4.5 × 10−3–2.1 × 10−2/site/year). The mean synonymous substitution rate in C2V3C3 was calculated to be 1.1 × 10−4–2.3 × 10−3/site/year (V3: 2.9 × 10−3/site/year). Among HIV-1 subtype B RNA-positive blood donors in Japan, the nucleotide substitution rate in C2V3C3 was estimated to be higher than that of reported cases using HIV-1 samples mainly obtained from AIDS patients. Compared to AIDS patients, immune responses against HIV-1 are probably more effective in HIV-1 RNA-positive blood donors. Consequently, immune pressure presumably promotes mutation of the virus genome.
KeywordsHIV-1 Nucleotide substitution rate Blood donor C2V3C3 region in the env gene Asymptomatic Treatment-naïve
NS and CM conceived the study; NS collected the data; NS performed data analysis and drafted the manuscript; all authors critically revised the manuscript for intellectual content. All authors read and approved the final manuscript. KM, TN, and MS are the guarantors of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose.
This study was conducted according to the principles in the Declaration of Helsinki. The Japanese Red Cross Blood Service ethics committee approved the study protocol (No. 2016-023-1).