Developmental Aspects of SARS-CoV-2, Potential Role of Exosomes and Their Impact on the Human Transcriptome

Abstract

With over 4.8 million deaths within 2 years, time is of the essence in combating COVID-19. The infection now shows devastating impacts on the younger population, who were not previously predicted to be vulnerable, such as in the older population. COVID-19-related complications have been reported in neonates whose mothers were infected with SARS-CoV-2 during pregnancy, and in children who get infected. Hence, a deeper understanding of the pathophysiology of COVID-19 during various developmental stages and placental transmission is essential. Although a connection has not yet been established between exosomal trafficking and the placental transmission of COVID-19, reports indicate that SARS-CoV-2 components may be trafficked between cells through exosomes. As the infection spreads, the transcriptome of cells is drastically perturbed, e.g., through the severe upregulation of several immune-related genes. Consequently, a major outcome of COVID-19 is an elevated immune response and the detection of viral RNA transcripts in host tissue. In this direction, this review focuses on SARS-CoV-2 virology, its in utero transmission from infected pregnant mothers to fetuses, SARS-CoV-2 and exosomal cellular trafficking, transcriptomic impacts, and RNA-mediated therapeutics against COVID-19. Future research will establish stronger connections between the above processes to develop diagnostic and therapeutic solutions towards COVID-19 and similar viral outbreaks.

Extracellular vesicles carry distinct proteo-transcriptomic signatures that are different from their cancer cell of origin

“…Subsequently, MVBs fuse with the plasma membrane resulting in the release of exosomes into the extracellular environment ( Johnstone et al., 1987 ; Trams et al., 1981 ). Nevertheless, exosomes are merely a subset of secretory EVs, other particles include—but are not limited to—apoptotic, micro-, onco-vesicles ( Kalluri and LeBleu, 2020 ; Kowal et al., 2014 ; Raposo and Stoorvogel, 2013 ), and exosome-like enveloped viruses ( Dogra et al., 2021 ). Accumulating evidence show that while all EVs carry molecular footprints from their cell of origin, exosomes selectively package proteins, nucleic acids, and do not appear enriched in cellular debris ( Kowal et al., 2014 ; Lotvall et al., 2014 ).…”

The human neurosecretome: extracellular vesicles and particles (EVPs) of the brain for intercellular communication, therapy, and liquid-biopsy applications

“…The viruses must also be considered as a subset of the vast EVP canopy ( Ghosh et al, 2020 ; Dogra et al, 2021 ). Many viruses follow the late lysosome or multivesicular body (MVB) followed by exocytosis mechanism for egress ( Alem et al, 2021 ; Dogra et al, 2021 ; Elmore et al, 2021 ). As shown by Dogra et al (202 1) the biogenesis of SARS-coV-2 have an egress pathway identical to the exosomes.…”

“…Many viruses follow the late lysosome or multivesicular body (MVB) followed by exocytosis mechanism for egress ( Alem et al, 2021 ; Dogra et al, 2021 ; Elmore et al, 2021 ). As shown by Dogra et al (202 1) the biogenesis of SARS-coV-2 have an egress pathway identical to the exosomes. While, other viruses, such as HIV, pinch off the plasma membrane ( Brügger et al, 2006 ).…”

“…From eukaryotes to prokaryotes, all cells secrete extracellular vesicles and particles (EVPs) as part of their regular homeostasis, intercellular communication, and cargo disposal ( Trams et al, 1981 ; Pan et al, 1985 ; Nieuwland and Sturk, 2010 ). These EVPs may include but are not limited to apoptotic bodies ( Kerr et al, 1972 ), ectosomes/microvesicles ( Dalton, 1975 ; Thery et al, 2018 ), exosomes ( Trams et al, 1981 ; Pegtel and Gould, 2019 ), mitochondria-derived vesicles ( D'Acunzo et al, 2021 ; Miller et al, 2022 ; Popov, 2022 ; Nakamya et al, 2022 ), exomeres ( Zhang et al, 2018 ), supermeres ( Zhang et al, 2021a ), high and low density-lipoproteins (HDL/LDL) ( Claude, 1970 ), ribonucleic proteins ( Barrieux et al, 1976 ), enveloped and non-enveloped viruses ( Dalton, 1975 ; Alem et al, 2021 ; Dogra et al, 2021 ), and other cell free proteins/DNA/RNA ( Figure 1 ) ( Lo, 2009 ; Mathivanan et al, 2010 ; Toden et al, 2020 ). Recent literature shows that EVPs carry distinct proteo-transcriptomic signatures from their cell of origin.…”

Associations and Disease–Disease Interactions of COVID-19 with Congenital and Genetic Disorders: A Comprehensive Review

“…Although it was suggested that congenital SARS-CoV-2 infection during early pregnancy could potentially trigger neurodevelopmental complications [ 178 ], no supporting evidence has been reported, so far. Furthermore, it was established that pregnant women are less likely to contract SARS-CoV-2 than the general public [ 189 ], and that the likelihood of SARS-CoV-2 vertical transmission is low [ 190 , 191 , 192 , 193 , 194 , 195 ]. For example, only 5.7% of 176 neonatal SARS-CoV-2 infections cases were classified as confirmed congenital infections [ 196 ].…”