From Plant Survival Under Severe Stress to Anti-Viral Human Defense – A Perspective That Calls for Common Efforts

Abstract

Reprogramming of primary virus-infected cells is the critical step that turns viral attacks harmful to humans by initiating super-spreading at cell, organism and population levels. To develop early anti-viral therapies and proactive administration, it is important to understand the very first steps of this process. Plant somatic embryogenesis (SE) is the earliest and most studied model for de novo programming upon severe stress that, in contrast to virus attacks, promotes individual cell and organism survival. We argued that transcript level profiles of target genes established from in vitro SE induction as reference compared to virus-induced profiles can identify differential virus traits that link to harmful reprogramming. To validate this hypothesis, we selected a standard set of genes named ‘ReprogVirus’. This approach was recently applied and published. It resulted in identifying ‘CoV-MAC-TED’, a complex trait that is promising to support combating SARS-CoV-2-induced cell reprogramming in primary infected nose and mouth cells. In this perspective, we aim to explain the rationale of our scientific approach. We are highlighting relevant background knowledge on SE, emphasize the role of alternative oxidase in plant reprogramming and resilience as a learning tool for designing human virus-defense strategies and, present the list of selected genes. As an outlook, we announce wider data collection in a ‘ReprogVirus Platform’ to support anti-viral strategy design through common efforts.

ROS/RNS Balancing, Aerobic Fermentation Regulation and Cell Cycle Control – a Complex Early Trait (‘CoV-MAC-TED’) for Combating SARS-CoV-2-Induced Cell Reprogramming

“…The sophisticated role of AOX in plants had developed along evolution in the context of complex holobiont systems. Currently, AOX is developed as a tool for understanding the functionality of its beneficial mechanisms also in mammals that naturally do not enclose AOX [see references in (21), in press]. It showed good integration into normal physiology when constitutively overexpressed in animals.…”

“…In a parallel perspective paper entitled 'From plant survival under severe stress to anti-viral human defense' we proposed using a standard profile of selected genes ('ReprogVirus') to trace early footprints of wide varieties of viruses under standardized in-vitro conditions (21). We raised and justified the hypothesis that transcript level profiles of justified target genes established from in vitro somatic embryogenesis (SE) induction in plants as a reference compared to virus-induced profiles can identify differential virus signatures that link to harmful reprogramming.…”

Adaptive Reprogramming During Early Seed Germination Requires Temporarily Enhanced Fermentation-A Critical Role for Alternative Oxidase Regulation That Concerns Also Microbiota Effectiveness

“…Furthermore, the data signaled activation of cell deathregulating system and arrested cell cycle by reducing alphatubulin gene transcription in the earliest step of reprogramming. Considering the generality of these observations, we proposed a reference transcriptome profile to identify virus traits that link to harmful reprogramming (Arnholdt-Schmitt et al, 2021). This approach helped to identify an early trait for combating SARS-CoV-2 that covers ROS/reactive nitrogen species (RNS) balancing, aerobic fermentation regulation, and cell cycle control (Costa et al, 2021).…”

Adaptive reprogramming during early seed germination requires temporarily enhanced fermentation – a critical role for alternative oxidase (AOX) regulation that concerns also microbiota effectiveness

“…Further, our data signaled activation of cell death-regulating system and arrested cell cycles at reduced alpha-tubulin transcription at the earliest step in reprogramming. Considering generality of these observations, we proposed a reference transcriptome profile to identify virus traits that link to harmful reprogramming (Arnholdt-Schmitt et al, 2021 In Press). This approach helped identifying an early trait for combating SARS-CoV-2 that covers ROS/RNS balancing, aerobic fermentation regulation and cell cycle control (Costa et al, 2021; preprint).…”

“…In Figure 2 , we present a simplified scheme that summarizes our conclusions based on wet-lab experiments, state-of-the-art knowledge and our hypothetical inferences related to the dynamic metabolic interplay between sucrose, aerobic fermentation, cyt respiration, AOX regulation/alternative respiration, and microbiota on cell reprogram functioning. In this scheme, we separate AOX as a macromolecule (gene/protein) from the functional pathway, the alternative respiration, to highlight the outstanding position of AOX as the key and only enzyme of a pathway that, if present in an organism, was recognized to provide a central metabolism-coordinating function for efficient survival (Mohanapriya et al, 2019, Arnholdt-Schmitt et al, 2021 In Press, Costa et al, 2021; preprint). We consider that under development- and/or environment-induced conditions of rapid sucrose increase, the Cyt pathway is stimulated via enhanced glycolysis, pyruvate production and increased TCA cycling in a way that the respiration chain can get overloaded by electrons followed by enhanced ROS/RNS levels and, on the other hand, restricted due to rapidly consumed oxygen and/or yet low numbers of functional mitochondria in relation to available oxygen during germination.…”