Does the Global Outbreak of COVID-19 or Other Viral Diseases Threaten the Stem Cell Reservoir Inside the Body?

Abstract

The COVID-19 pandemic has profoundly influenced public health and contributed to global economic divergences of unprecedented dimensions. Due to the high prevalence and mortality rates, it is then expected that the consequence and public health challenges will last for long periods. The rapid global spread of COVID-19 and lack of enough data regarding the virus pathogenicity multiplies the complexity and forced governments to react quickly against this pandemic. Stem cells represent a small fraction of cells located in different tissues. These cells play a critical role in the regeneration and restoration of injured sites. Because of their specific niche and a limited number of stem cells, the key question is whether there are different anti-viral mechanisms against viral infection notably COVID-19. Here, we aimed to highlight the intrinsic antiviral resistance in different stem cells against viral infection. These data could help us to understand the possible viral infections in different stem cells and the activation of specific molecular mechanisms upon viral entrance.

Keywords: Anti-viral defense system; COVID-19; Mature cells; Stem cells.

Fig. 1

SARS-CoV-2 is encased within a fatty membrane (envelop) and has a very large genomic pool with nucleotides around 3 × 10⁴. The viral structure is composed of membrane protein, nucleoprotein, envelope small membrane protein, hemagglutinin, single-strand positive sensel RNA, and spike glycoprotein (a). Two types of cup-shaped spike glycoproteins subunits S1 and S2 are present on the viral surface which attach the viral body to the host cellular receptor ACE-2 (b). Membrane protein = M; Nucleoprotein = N; Envelope small membrane protein = E; and Hemagglutinin = HE. The illustration was created with BioRender.com

Fig. 2

The proliferation of SARS-CoV-2 within the host cells initiates soon after attachment of S protein (S1 and S2) to the cell membrane-bound ACE-2 receptor. Allosteric changes in S protein promote viral envelope fusion with the cell membrane through endosomal signaling. Inside the cells, the genomic pool is released, transcribed, and translated to synthesize various components of viral structure. Finally, viral proteins and genome RNA are assembled into virions in the endoplasmic reticulum and Golgi apparatuses and transported into microvacuoles. In the next, step, the microvesicles containing virions are released. After infection of host cells with COVID-19 nanoparticles, the release of virions promotes pyroptosis and massive cellular damage. The neighboring cells such as endothelial cells, dust cells (alveolar macrophages) start to release an array of cytokines and chemokines. With the progression of cellular damage, blood lymphocytes (either T and B), as well as macrophages, are recruited to the site of infection. Accumulation of immune cells exacerbates the inflammatory responses by the continuous production of inflammatory cytokines. Interleukine 10: IL-10; Interleukine 6: IL-6; granulocyte colony-stimulating factor: G-CSF; Macrophage inflammatory protein 1α: MIP1α; Interferon-gamma: IFNγ; Interleukine 2: IL-2; Tumour necrosis factor-α: TNF-α. The illustration was created with BioRender.com

Fig. 3

different intracellular mechanisms used by stem cells to inhibit the proliferation and expansion inside these cells. The illustration was created with BioRender.com

Fig. 4

Cross-talk between TLRs and NrF2 signaling pathways in the viral infection. Endosomal TLRs including TLR 3,4,7,8,9 recognize the viral ssRNA and dsRNA. Stimulation of TLR7 by viral RNAs causes the production of NADPH oxidase which is an imperative factor in the connection of two signaling pathways and in results activation of NrF2 downstream pathways. Additionally, activation of TLR3 leads to the production of other anti-oxidant elements related to NrF2 pathways such as HO-1, which participates in the activation process of stress response transcription factors including NrF2, NF-KB, and AP-1. TLR 3 and 7 also appreciate the initiation of autophagy which can deliver the nucleic acid fragments of viruses to the endosomal TLRs and leads them to degradation by recruiting autolysosomes. On the other hand, NrF2 signaling pathways are in a relationship with the stemness of stem cells by inhibiting the activation of OCT4 and NANOG proteins by using ubiquitin/proteasome. The illustration was created with BioRender.com

Fig. 5

The similarity in exosome biogenesis and virus assembly system makes virus to use exosome biogenesis pathways for delivery and cell exit. The illustration was created with BioRender.com