New coronavirus appears to change its pathogenic mutation In vitro infection shows a maximum difference of 270 times

Scientific studies to date have shown that the new coronavirus (SARS-CoV-2) has mutated, and it is not clear what effect the mutation will haveApril 20, led by Chinese Academy of Engineering academician Li Lanxuan published in the pre-printed website medRxiv (not peer-reviewed) a study report that SARS-CoV-2 has been able to substantially change its pathogenic function of the mutation, and the difference in viral load of different mutated strains can be up to 270 timeshttps://doi.org/10.1101/2020.04.14.20060160researchers collected virus samples from 11 COVID-19 patients admitted to Zhejiang University Hospital between January 22, 2020 and February 4, 2020Of these, 8 were male patients and 3 were female patients, aged between 4 months and 71 years old, with the exception of the youngest patients with mild symptoms, the remaining 10 patients were moderate or severe patientsto explore the mutation spectrum of the 11 virus isolates, the researchers sequenced the 11 virus isolates at a depth level and compared the results with 1,111 genome sequences in the Global Shared Influenza Data Initiative (GISAID), and found that these isolated strains coexisted in 33 mutations, 19 of which were new mutations found for the first timeAlthough the sample size is small, the analysis shows that the virus has a rich variability of variation, indicating that the true diversity of the new coronary strain is largely understoodsummed up with each mutation in 11 virus isolates, the blue marker means a new mutation
but the most critical question is, how will the mutation affect the pathogenic function of the virus?Because COVID-19 patients may develop different symptoms of infection due to age, physical condition, etc., the researchers chose Vero-E6 cell lines for in vitro infection testing in order to assess more objectively the effects of these mutations on the pathogenicity of the virusThis cell line OF ACE2 protein is very similar to the human body, and ACE2 is the receptor required for SARS-CoV-2 to enter human cells, thus providing direct evidence of SARS-CoV-2 infection cell linesresearchers infected Vero-E6 cells with the SARS-CoV-2 strains taken from the 11 patients, and then at regular intervals collected the cells and detected the cell's viral loadThe observation results show that over time, the new coronavirus strain shows significant difference in viral load, and on this node in 24 hours, the virus load of different virus strains can vary up to 270 times!When Vero-E6 cells are infected, there is a time-change in the viral load of the PATIENT-derived SARS-CoV-2 isolated strainSo, does the higher viral load mean a greater risk of cell death?In the next experiment, the researchers used a DIC microscope to observe the effect of cell lesions (CPE) on the 48-hour and 72-hour time nodes, a condition in which the virus multiplys in large numbers, causing cell lesions and even deathThe results show that CPE is highly consistent with the viral load data, which shows that the higher the viral load, the higher the cell mortality rate changes in CPE are closely related to viral load (CT) A a significant change in viral load was observed at each point in time, the cells referred to by the arrow in B were dissolving and C was the relationship between CPE and CT noted that the virus strains isolated from patient No 11 (ZJU-11) had a three-nucleotide mutation, and that the mutation appeared to significantly improve the replication rate and pathogenicity of the strain in subsequent experiments, with the patient's positive test results maintained for 45 days The researchers believe that the effects of this mutation on the pathogenic function of the virus are worth studying , this study provides direct evidence that mutations currently occurring in the SARS-CoV-2 genome have functional potential to affect the pathogenicity of the virus Therefore, in addition to accumulating genome sequencing data, researchers should monitor viruses at the cellular level as much as possible Although the development of COVID-19 drugs and vaccines is imminent, these cumulative mutations need to be taken into account to avoid potential pitfalls References: 1 - Patient-derived mutations as coscosofedity of SARS-CoV-2.
Li Lanxuan's new paper: Find 19 pathogenic new mutations of the new coronavirus! original title: Li Lanxuan Team: SARS-CoV-2 appears mutation that can change its pathogenicity, in vitro infection shows up to 270 times difference