Statistical analysis supports UTR (untranslated region) deletion theory in SARS-CoV-2

Xu, Zhaobin; Yang, Dan; Wang, Liyan; Demongeot, Jacques

doi:10.1080/21505594.2022.2132059

Cited by 9 publications

(4 citation statements)

References 59 publications

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“…Our model demonstrated that the attenuated virus with proliferation constraints (smaller

value in our model) could induce the immune response and antibody level in a milder way (shown in Figure 5 ). Those attenuated live viruses form a solid basis for asymptomatic infections [ 87 ]. There are at least two remarkable advantages of attenuated live viruses in future vaccine development.…”

Section: Discussionmentioning

confidence: 99%

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

Wei

Zhang

et al. 2023

Viruses

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Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on a comprehensive understanding of immunology principles. This model explicitly formulizes the pernicious effect of the antibody, together with a positive feedback stimulation of the virus–antibody complex on the antibody regeneration. Besides providing quantitative insights into antibody and virus dynamics, it demonstrates good adaptivity in recapturing the virus-antibody interaction. It is proposed that the environmental antigenic substances help maintain the memory cell level and the corresponding neutralizing antibodies secreted by those memory cells. A broader application is also visualized in predicting the antibody protection time caused by a natural infection. Suitable binding antibodies and the presence of massive environmental antigenic substances would prolong the protection time against breakthrough infection. The model also displays excellent fitness and provides good explanations for antibody selection, antibody interference, and self-reinfection. It helps elucidate how our immune system efficiently develops neutralizing antibodies with good binding kinetics. It provides a reasonable explanation for the lower SARS-CoV-2 mortality in the population that was vaccinated with other vaccines. It is inferred that the best strategy for prolonging the vaccine protection time is not repeated inoculation but a directed induction of fast-binding antibodies. Eventually, this model will inform the future construction of an optimal mathematical model and help us fight against those infectious diseases.

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“…Our model demonstrated that the attenuated virus with proliferation constraints (smaller

Section: Discussionmentioning

confidence: 99%

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

Wei

Zhang

et al. 2023

Viruses

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“…When the value of p is large, the population’s evolution can still rapidly progress irreversibly towards loss of virulence. In our previous research articles [31], we suggested that the rapid disappearance of SARS and MERS may be attributed to this phenomenon, as truncation of the two UTRs is a common way to generate defective viruses with weak replication activity.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatic Analysis of Defective Viral Genomes in SARS-CoV-2 and Its Impact on Population Infection Characteristics

Xu,

Peng,

Song

et al. 2023

Preprint

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DVGs (Defective Viral Genomes) and SIP (Semi-Infectious Particle) are commonly present in RNA virus infections. In this study, we analyzed high-throughput sequencing data and found that DVGs or SIPs are also widely present in SARS-CoV-2. Comparison of SARS-CoV-2 with various DNA viruses revealed that the SARS-CoV-2 genome is more susceptible to damage and has greater sequencing sample heterogeneity. Variability analysis at the whole-genome sequencing depth showed a higher coefficient of variation for SARS-CoV-2, and DVG analysis indicated a high proportion of splicing sites, suggesting significant genome heterogeneity and implying that most virus particles assembled are enveloped with incomplete RNA sequences. We further analyzed the characteristics of different strains in terms of sequencing depth and DVG content differences and found that as the virus evolves, the proportion of intact genomes in virus particles increases, which can be significantly reflected in third-generation sequencing data, while the proportion of DVG gradually decreases. Specifically, the proportion of intact genome of Omicron was greater than that of Delta and Alpha strains. This can well explain why Omicron strain is more infectious than Delta and Alpha strains. We also speculate that this improvement in completeness is due to the enhancement of virus assembly ability, as the Omicron strain can quickly realize the binding of RNA and capsid protein, thereby shortening the exposure time of exposed virus RNA in the host environment and greatly reducing its degradation level. Finally, by using mathematical modeling, we simulated how DVG effects under different environmental factors affect the infection characteristics and evolution of the population. We can explain well why the severity of symptoms is closely related to the amount of virus invasion and why the same strain causes huge differences in population infection characteristics under different environmental conditions. Our study provides a new approach for future virus research and vaccine development.

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“…strain was also in the 2B protein of the P2 region. Moreover, as studies showed that mutations and deletions in the UTR of some viruses are associated with replication and virulence (41)(42)(43)(44)(45), the single nucleotide difference between the two strains from the CSF and oropharyngeal swab samples in the 5 UTR of echovirus 18 merits further investigation.…”

Section: Discussionmentioning

confidence: 99%

Case report: Clinical and virological characteristics of aseptic meningitis caused by a recombinant echovirus 18 in an immunocompetent adult

Jiang

Zhou

et al. 2023

Front. Med.

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Echovirus 18 has been recognized as an important causative pathogen of aseptic meningitis in young children worldwide, and echovirus 18-induced meningitis is rarely found in adults with immunocompetence. In this case study, we report the clinical and virological characteristics of aseptic meningitis caused by recombinant echovirus 18 in an adult with immunocompetence. A 31-year-old woman with immunocompetence was admitted to our hospital with fever, dizziness, severe headache, nausea, and vomiting for the past 1 day and was diagnosed with viral meningitis based on the clinical manifestations and laboratory results from cerebrospinal fluid (CSF). The patient received antiviral treatment with ribavirin and interferon as soon as the enterovirus infection was identified using qRT-PCR and was cured after 4 days. From the oropharyngeal swab and CSF samples, two echovirus 18 strains were isolated with a single nucleotide difference located at the 5′ UTR. Phylogenetic analyses based on the VP1 gene showed that the two strains belonged to the subgenotype C2 and were clustered with sequences obtained from China after 2015, while the results from the 3D polymerase region showed that the two strains were closely related to the E30 strains. Bootscanning results using the 5′ UTR to 2A region and the 2B to 3′ UTR region showed that potential intertypic recombination had occurred in the 2B gene. Recombination analyses further confirmed that the two strains (echovirus 18) presented genome recombination with echovirus 30 in the nucleotide regions of the 2B gene. To the best of our knowledge, this is the first report of echovirus 18-induced meningitis in an adult with immunocompetence from mainland China, highlighting the need for close surveillance of echovirus 18 both in children and adults in the future.

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Statistical analysis supports UTR (untranslated region) deletion theory in SARS-CoV-2

Cited by 9 publications

References 59 publications

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

Bioinformatic Analysis of Defective Viral Genomes in SARS-CoV-2 and Its Impact on Population Infection Characteristics

Case report: Clinical and virological characteristics of aseptic meningitis caused by a recombinant echovirus 18 in an immunocompetent adult

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