In a perspective entitled 'From plant survival under severe stress to anti-viral human defense' 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. A standard profile of selected genes named 'ReprogVirus' was proposed for in vitro-scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the 'ReprogVirus platform' was initiated. This initiative aims to identify in a common effort across scientific boundaries critical virus footprints from diverse virus origins and variants as a basis for anti-viral strategy design. This approach is open for validation and extension. In the present study, we initiated validation by experimental transcriptome data available in public domain combined with advancing plant wet lab research. We compared plant-adapted transcriptomes according to 'RegroVirus' complemented by alternative oxidase (AOX) genes during de novo programming under SE-inducing conditions with in vitro corona virus-induced transcriptome profiles. This approach enabled identifying a major complex trait for early de novo programming during SARS-CoV-2 infection, called 'CoV-MAC-TED'. It consists of unbalanced ROS/RNS levels, which are connected to increased aerobic fermentation that links to alpha-tubulin-based cell restructuration and progression of cell cycle. We conclude that anti-viral/anti-SARS-CoV-2 strategies need to rigorously target 'CoV-MAC-TED' in primary infected nose and mouth cells through prophylactic and very early therapeutic strategies. We also discuss potential strategies in the view of the beneficial role of AOX for resilient behavior in plants. Furthermore, following the general observation that ROS/RNS equilibration/redox homeostasis is of utmost importance at the very beginning of viral infection, we highlight that 'de-stressing' disease and social handling should be seen as essential part of anti-viral/anti-SARS-CoV-2 strategies.

/pdf/ros-rns-balancing-aerobic-fermentation-regulation-and-cell-1qdbjj6qaq.pdf

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.

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.

/pdf/from-plant-survival-under-severe-stress-to-anti-viral-human-2frbf7za1q.pdf

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

BackgroundTranscriptome studies of a selected gene set (ReprogVirus) had identified unbalanced ROS/RNS levels, which connected to increased aerobic fermentation that linked to alpha-tubulin-based cell restructuration and cell cycle control, as a major complex trait for early de novo programming (CoV-MAC-TED) upon SARS-CoV-2 infection. Recently, CoV-MAC-TED was confirmed as promising marker by using primary target human nasal epithelial cells (NECs) infected by two SARS-CoV-2 variants with different effects on disease severity. To further explore this marker/cell system as a standardized tool for identifying anti-viral targets in general, testing of further virus types is required. Results: Transcriptome level profiles of H3N2 influenza-infected NECs indicated ROS/RNS level changes and increased transcript accumulation of genes related to glycolysis, lactic fermentation and -tubulin at 8 hours post infection. These early changes linked to energy-dependent, IRF9-marked rapid immunization. However, ReprogVirus-marker genes indicated the absence of initial cell cycle progress, which contrasted our findings during infections with two SARS-CoV-2 variants, where cell cycle progress was linked to delayed IRF9 response. Our results point to the possibility of CoV-MAC-TED-assisted, rapid individual host cell response identification upon virus infections. Conclusion: The complex trait CoV-MAC-TED can identify similar and differential early responses of SARS-CoV-2 and influenza H3N2 viruses. This indicates its appropriateness to search for anti-viral targets in view of therapeutic design strategies. For standardization, human NECs can be used. This marker/cell system is promising to identify differential early cell responses upon viral infections also depending on cell origins.

https://biorxiv.org/content/10.1101/2021.10.18.464828v1.full.pdf

Transcriptome data from human nasal epithelial cells infected by H3N2 influenza virus indicate early unbalanced ROS/RNA levels, temporarily increased aerobic fermentation linked to enhanced α-tubulin and rapid energy-dependent IRF9-marked immunization

In a perspective entitled From plant survival under severe stress to anti-viral human defense 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. A standard profile of selected genes named ReprogVirus was proposed for in vitro-scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the ReprogVirus platform was initiated. This initiative aims to identify in a common effort across scientific boundaries critical virus footprints from diverse virus origins and variants as a basis for anti-viral strategy design. This approach is open for validation and extension. In the present study, we initiated validation by experimental transcriptome data available in public domain combined with advancing plant wet lab research. We compared plant-adapted transcriptomes according to RegroVirus complemented by alternative oxidase (AOX) genes during de novo programming under SE-inducing conditions with in vitro corona virus-induced transcriptome profiles. This approach enabled identifying a major complex trait for early de novo programming during SARS-CoV-2 infection, called CoV-MAC-TED. It consists of unbalanced ROS/RNS levels, which are connected to increased aerobic fermentation that links to alpha-tubulin-based cell restructuration and progression of cell cycle. We conclude that anti-viral/anti-SARS-CoV-2 strategies need to rigorously target CoV-MAC-TED in primary infected nose and mouth cells through prophylactic and very early therapeutic strategies. We also discuss potential strategies in the view of the beneficial role of AOX for resilient behavior in plants. Furthermore, following the general observation that ROS/RNS equilibration/redox homeostasis is of utmost importance at the very beginning of viral infection, we highlight that de-stressing disease and social handling should be seen as essential part of anti-viral/anti-SARS-CoV-2 strategies.

/pdf/ros-rns-balancing-aerobic-fermentation-regulation-and-cell-2b5disdjr4.pdf

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

Plants respond to environmental cues via adaptive cell reprogramming that can affect whole plant and ecosystem functionality. Microbiota constitutes part of plant’s inner and outer environment. This Umwelt underlies steady dynamics, due to complex local and global biotic and abiotic changes. Hence, adaptive plant holobiont responses are crucial for continuous metabolic adjustment at systems levels. Plants require oxygen-dependent respiration for energy-dependent adaptive morphology, such as, germination, root and shoot growth, formation of adventitious, clonal and reproductive organs, fruits and seeds. Fermentative paths can help in acclimation and, to our view the role of alternative oxidase (AOX) in coordinating complex metabolic and physiologic adjustments is underestimated. Cellular level of sucrose is an important sensor of environmental stress. We explored the role of exogenous sucrose and its interplay with AOX during early seed germination. We found that sucrose-dependent initiation of fermentation during the first 12 hours after imbibition (HAI) was beneficial to germination. However, parallel enhanced AOX expression was essential to control negative effects by prolonged sucrose treatment. Early down-regulated AOX activity until 12 HAI improved germination efficiency in the absence of sucrose, but suppressed early germination in its presence. Our results also suggest that seeds-inoculated arbuscular mycorrhizal fungi can buffer sucrose stress during germination to restore normal respiration more efficiently. Following this approach, we propose a simple method to identify organic seeds and low-cost on-farm perspectives for early selection on disease tolerance, predicting plant holobiont behavior and improving germination. Furthermore, our research strengthens the view that AOX can serve as powerful functional marker source for seed hologenomes.

/pdf/adaptive-reprogramming-during-early-seed-germination-22naxihvux.pdf

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

Alok Adhloeya

Papers

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

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