Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models

Eun-Ha Hwang; Hoyin Chung; Green Kim; Hanseul Oh; You Jung An; Philyong Kang; Choong-Min Ryu; Jong-Hwan Park; Jungjoo Hong; Bon-Sang Koo

doi:10.3389/fmicb.2021.694897

Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models

Front Microbiol. 2021 Jul 9:12:694897. doi: 10.3389/fmicb.2021.694897. eCollection 2021.

Authors

Eun-Ha Hwang^{1

2}, Hoyin Chung^{1

3}, Green Kim^{1

2}, Hanseul Oh¹, You Jung An¹, Philyong Kang⁴, Choong-Min Ryu⁵, Jong-Hwan Park², Jungjoo Hong¹, Bon-Sang Koo¹

Affiliations

¹ National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea.
² Laboratory of Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
³ Department of Microbiology, College of Natural Sciences, Chungbuk National University, Cheongju, South Korea.
⁴ Futuristic Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea.
⁵ Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.

Abstract

Recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. In this report, we performed deep sequencing for seed virus and SARS-CoV-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucleotide polymorphisms (SNPs) in SARS-CoV-2 by variant analysis. A total of 69 single-nucleotide variants (SNVs) were present in the 5'-untranslated region (UTR), 3'-UTR, ORF1ab, S, ORF3a, ORF8, and N genes of the seed virus passaged in VERO cells. Between those present on the seed virus and those on each SARS-CoV-2 isolated from the lungs of the macaques, a total of 29 variants was identified in 4 coding proteins (ORF1ab, S, ORF3a, and N) and non-coding regions (5'- and 3'-UTR). Variant number was significantly different according to individuals and ranged from 2 to 11. Moreover, the average major frequency variation was identified in six sites between the cynomolgus monkeys and rhesus macaques. As with diverse SNPs in SARS-CoV-2, the values of viral titers in lungs were significantly different according to individuals and species. Our study first revealed that the genomes of SARS-CoV-2 differ according to individuals and species despite infection of the identical virus in non-human primates (NHPs). These results are important for the interpretation of longitudinal studies evaluating the evolution of the SARS-CoV-2 in human beings and development of new diagnostics, vaccine, and therapeutics targeting SARS-CoV-2.

Keywords: SARS-CoV-2; genetic variants; non-human primate; single nucleotide polymorphism; single nucleotide variant.