Effects of Cell Proteostasis Network on the Survival of SARS-CoV-2

Abstract

The proteostasis network includes all the factors that control the function of proteins in their native state and minimize their non-functional or harmful reactions. The molecular chaperones, the important mediator in the proteostasis network can be considered as any protein that contributes to proper folding and assembly of other macromolecules, through maturating of unfolded or partially folded macromolecules, refolding of stress-denatured proteins, and modifying oligomeric assembly, otherwise it leads to their proteolytic degradation. Viruses that use the hosts’ gene expression tools and protein synthesis apparatus to survive and replicate, are obviously protected by such a host chaperone system. This means that many viruses use members of the hosts’ chaperoning system to infect the target cells, replicate, and spread. During viral infection, increase in endoplasmic reticulum (ER) stress due to high expression of viral proteins enhances the level of heat shock proteins (HSPs) and induces cell apoptosis or necrosis. Indeed, evidence suggests that ER stress and the induction of unfolded protein response (UPR) may be a major aspect of the corona-host virus interaction. In addition, several clinical reports have confirmed the autoimmune phenomena in COVID-19-patients, and a strong association between this autoimmunity and severe SARS-CoV-2 infection. Part of such autoimmunity is due to shared epitopes among the virus and host. This article reviews the proteostasis network and its relationship to the immune system in SARS-CoV-2 infection.

Human genetic basis of coronavirus disease 2019

“…SARS-CoV-2 is an enveloped, non-segmented, positive-sense single-stranded RNA virus with 29,903 nucleotides in its genome sequence containing 5′ capped and 3′ polyadenylated. 41 – 43 The 5′ two-thirds region of the genome is occupied by two large open reading frames (ORFs), ORF1a and ORF1b, that encodes 15–16 nonstructural proteins. 44 Other functional ORFs encode structural and accessory proteins.…”

Estrés celular y SARS-CoV-2.

“…Además hay que considerar la gemación de CoV, que después de múltiples replicaciones conduce a su liberación del RE al compartimento intermedio de Golgi (ERGIC) de la célula huésped. La gemación da como resultado el agotamiento de los lípidos de la membrana del RE, afecta la integridad del RE y, por lo tanto, aumenta el estrés del RE (42,43).…”

Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)

“…Viruses can directly control UPR responses with their proteins, which can decrease the host’s antiviral response and is a key aspect of the coronavirus–host relationship [ 274 ]. Indeed, data suggest that ER stress and UPR activation are important aspects of CoV virus–host cell interactions [ 275 ]. The virus finds the mechanisms it needs to reproduce inside the cell, such as a protein quality control system that includes HSPs, which, in addition to their physiological roles, assist in viral protein stabilization.…”