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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Immunity, virus evolution, and effectiveness of SARS-CoV-2 vaccines

Full text
Author(s):
J.E. Belizário [1]
Total Authors: 1
Affiliation:
[1] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil
Total Affiliations: 1
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 54, n. 5 2021-03-15.
Abstract

Phylogenetic and pathogenesis studies of the severe acute respiratory syndrome-related coronaviruses (SARS-CoVs) strains have highlighted some specific mutations that could confer the RNA genome fitness advantages and immunological resistance for their rapid spread in the human population. The analyses of 30 kb RNA SARS-CoVs genome sequences, protein structures, and functions have provided us a perspective of how host-virus protein-protein complexes act to mediate virus infection. The open reading frame (ORF)1a and ORF1b translation yields 16 non-structural (nsp1-16) and 6 accessory proteins (p6, p7a, p8ab, p9b) with multiple functional domains. Viral proteins recruit over 300 host partners forming hetero-oligomeric complexes enabling the viral RNA synthesis, packing, and virion release. Many cellular host factors and the innate immune cells through pattern-recognition receptors and intracellular RNA sensor molecules act to inhibit virus entry and intracellular replication. However, non-structural ORF proteins hijack them and suppress interferon synthesis and its antiviral effects. Pro-inflammatory chemokines and cytokines storm leads to dysfunctional inflammation, lung injury, and several clinical symptoms in patients. During the global pandemic, COVID-19 patients were identified with non-synonymous substitution of G614D in the spike protein, indicating virus co-evolution in host cells. We review findings that suggest that host RNA editing and DNA repair systems, while carrying on recombination, mutation, and repair of viral RNA intermediates, may facilitate virus evolution. Understanding how the host cell RNA replication process may be driven by SARS-CoV-2 RNA genome fitness will help the testing of vaccines effectiveness to multiple independent mutated coronavirus strains that will emerge. (AU)

FAPESP's process: 18/08540-8 - Immnunotherapy to target cancer stem cell subpopulations in oral squamous cell carcinoma: the role of natural killer cells
Grantee:Maria Fernanda Setúbal Destro Rodrigues
Support Opportunities: Regular Research Grants