Emerging SARS-CoV-2 Genotypes Show Different Replication Patterns in Human Pulmonary and Intestinal Epithelial Cells.

Gabriel Augusto Pires De Souza,Marion Le Bideau,Lorène Ferreira,Nathalie Wurtz,Philippe Colson,Celine Boschi,Christian Devaux,Bernard La Scola

doi:10.3390/v14010023

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) quickly spread worldwide following its emergence in Wuhan, China, and hit pandemic levels. Its tremendous incidence favoured the emergence of viral variants. The current genome diversity of SARS-CoV-2 has a clear impact on epidemiology and clinical practice, especially regarding transmission rates and the effectiveness of vaccines. In this study, we evaluated the replication of different SARS-CoV-2 isolates representing different virus genotypes which have been isolated throughout the pandemic. We used three distinct cell lines, including Vero E6 cells originating from monkeys; Caco-2 cells, an intestinal epithelium cell line originating from humans; and Calu-3 cells, a pulmonary epithelium cell line also originating from humans. We used RT-qPCR to replicate different SARS-CoV-2 genotypes by quantifying the virus released in the culture supernatant of infected cells. We found that the different viral isolates replicate similarly in Caco-2 cells, but show very different replicative capacities in Calu-3 cells. This was especially highlighted for the lineages B.1.1.7, B.1.351 and P.1, which are considered to be variants of concern. These results underscore the importance of the evaluation and characterisation of each SARS-CoV-2 isolate in order to establish the replication patterns before performing tests, and of the consideration of the ideal SARS-CoV-2 genotype–cell type pair for each assay.

Highlights

A newly-emerging coronavirus that infects humans was reported in December 2019 in patients presenting with viral pneumonia in Wuhan, China [1]
Vero E6 cells were established from kidney tissue sampled from an African green monkey, and are a mammalian cell line which is widely used for the isolation and production of viruses, including SARS-CoV-2, as these cells abundantly express ACE2 and allow the complete replication cycle of the virus [32,33,34]
The current genome diversity of SARS-CoV-2 has a clear impact on clinical practice, especially regarding transmission rates and the effectiveness of vaccines, making it difficult to effectively combat COVID-19

Summary

Introduction

A newly-emerging coronavirus that infects humans was reported in December 2019 in patients presenting with viral pneumonia in Wuhan, China [1]. Coronaviruses are enveloped viruses, with a positive single-stranded RNA genome and various host animals [2]. They are divided into four genera: alpha, beta, gamma, and delta [3]. Only alpha and beta coronaviruses are known to infect humans, leading to pathologies ranging from symptoms typical of the common cold to life-threatening respiratory diseases in the lower respiratory tract [3]. Before this new coronavirus was identified in China, only six human pathogenic coronaviruses were known [2].

Results

Discussion

Conclusion