tenOever, B. R. | Search bioRxiv

bioRxiv2020

SARS-CoV-2 launches a unique transcriptional signature from in vitro, ex vivo, and in vivo systems

One of the greatest threats to humanity is the emergence of a pandemic virus. Among those with the greatest potential for such an event include influenza viruses and coronaviruses. In the last century alone, we have observed four major influenza A virus pandemics as well as the emergence of three highly pathogenic coronaviruses including SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic. As no effective antiviral treatments or vaccines are presently available against SARS-CoV-2, it is important to understand the host response to this virus as this may guide the efforts in development towards novel therapeutics. Here, we offer the first in-depth characterization of the host transcriptional response to SARS-CoV-2 and other respiratory infections through in vitro, ex vivo, and in vivo model systems. Our data demonstrate the each virus elicits both core antiviral components as well as unique transcriptional footprints. Compared to the response to influenza A virus and respiratory syncytial virus, SARS-CoV-2 elicits a muted response that lacks robust induction of a subset of cytokines including the Type I and Type III interferons as well as a numerous chemokines. Taken together, these data suggest that the unique transcriptional signature of this virus may be responsible for the development of COVID-19.

microbiology↗

bioRxiv2019

Rapid dissemination and monopolization of viral populations in mice revealed using a panel of barcoded viruses

The gastrointestinal tract presents a formidable barrier for pathogens to initiate infection. Despite this barrier, enteroviruses, including coxsackievirus B3 (CVB3), successfully penetrate the intestine to initiate infection and spread systemically prior to shedding in stool. However, the effect of the gastrointestinal barrier on CVB3 population dynamics is relatively unexplored, nor are the selective pressures acting on CVB3 in the intestine well-characterized. To examine viral population dynamics in orally infected mice, we produced over one hundred CVB3 viruses harboring unique nine nucleotide \"barcodes.\" Using this collection of barcoded viruses, we found diverse viral populations throughout each mouse within the first day post-infection, but by 48 hours the viral populations were dominated by less than three barcoded viruses in intestinal and extra-intestinal tissues. Using light-sensitive viruses to track replication status, we found diverse viruses had replicated prior to loss of diversity. Sequencing whole viral genomes from samples later in infection did not reveal detectable viral adaptations. Surprisingly, orally inoculated CVB3 was detectable in pancreas and liver as soon as 20 minutes post inoculation, indicating rapid systemic dissemination. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues. These results underscore a complex dynamic between dissemination and clearance for an enteric virus.\n\nImportanceEnteric viruses initiate infection in the gastrointestinal tract but can disseminate to systemic sites. However, the dynamics of viral dissemination are unclear. In this study, we created a library of 135 barcoded coxsackieviruses to examine viral population diversity across time and space following oral inoculation of mice. Overall, we found that the broad population of viruses disseminates early, followed by monopolization of mouse tissues with three or fewer pool members at later time points. Interestingly, we detected virus in systemic tissues such as pancreas and liver just 20 minutes post-oral inoculation. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues.

microbiology↗