The aim of the study is to analyze viruses using parameters obtained from distributions of nucleotide sequences in the viral RNA. Seeking for the input data homogeneity, we analyze single-stranded RNA viruses only. Two approaches are used to obtain the nucleotide sequences; In the first one, chunks of equal length are considered. In the second approach, the whole RNA genome is divided into parts by adenine or the most frequent nucleotide as a “space”. Rank–frequency distributions are studied in both (...) cases. The defined nucleotide sequences are signs comparable to a certain extent to syllables or words as seen from the nature of their rank–frequency distributions. Within the first approach, the Pólya and the negative hypergeometric distribution yield the best fit. For the distributions obtained within the second approach, we have calculated a set of parameters, including entropy, mean sequence length, and its dispersion. The calculated parameters became the basis for the classification of viruses. We observed that proximity of viruses on planes spanned on various pairs of parameters corresponds to related species. In certain cases, such a proximity is observed for unrelated species as well calling thus for the expansion of the set of parameters used in the classification. We also observed that the fifth most frequent nucleotide sequences obtained within the second approach are of different nature in case of human coronaviruses. We expect that our findings will be useful as a supplementary tool in the classification of diseases caused by RNA viruses with respect to severity and contagiousness. (shrink)

Many viruses evolved mechanisms for capping the 5′‐ends of their plus‐strand RNAs as a means of hijacking the eukaryotic messenger RNA (mRNA) splicing/translation machinery. Although capping is critical for replication, the RNAs of these viruses have other essential functions including their requirement to be packaged as either genomes or pre‐genomes into progeny viruses. Recent studies indicate that human immunodeficiency virus type‐1 (HIV‐1) RNAs are segregated between splicing/translation and packaging functions by a mechanism that involves structural sequestration of the 5′‐cap. Here, (...) we examined studies reported for other viruses and retrotransposons that require both selective packaging of their RNAs and 5′‐RNA capping for host‐mediated translation. Our findings suggest that viruses and retrotransposons have evolved multiple mechanisms to control 5′‐cap accessibility, consistent with the hypothesis that removal or sequestration of the 5′ cap enables packageable RNAs to avoid capture by the cellular RNA processing and translation machinery. (shrink)

The majority of human, animal and plant viral pathogens possess genomes composed of RNA. The strategies evolved for expression and replication of viral RNA genomes can differ significantly from those utilized for expression and replication of host‐cell genetic material. Consequently, knowledge of the molecular details of these strategies can lead to a clearer understanding of the origin, evolution and control of viral pathogens. We describe recent progress in identifying important structural and functional domains of the RNA genomes (...) and associated replicative enzymes for two very different viruses: vesicular stomatitis virus, which possesses a single‐stranded RNA genome of negative polarity, and wound tumor virus, which contains a genome composed of 12 discrete segments of double‐stranded RNA. (shrink)

In plants, virus‐derived double‐stranded RNA is processed into small interfering (si)RNAs by RNAse III‐type enzymes. siRNAs are believed to guide an RNA‐induced silencing complex (RISC) to promote sequence‐specific degradation (or ‘slicing’) of homologous viral transcripts. This process, called RNA silencing, likely involves Argonaute (AGO) proteins that are known components of plant and animal RISCs. Plant viruses commonly counteract the silencing immune response by producing suppressor proteins, but the molecular basis of their action has remained largely unclear. A recent study (...) by Zhang and colleagues1 now shows that the 2b suppressor of Cucumber mosaic virus directly interacts with Arabidopsis AGO1 and inhibits its slicing activity, suggesting that AGO1 might be a component of the elusive plant antiviral RISC. BioEssays 29:319–323, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Polioviruses of reduced neurovirulence contain point mutations in the viral RNA that are responsible for the attenuated phenotype. Two such point mutations have been identified in the genomes of the Sabin live oral vaccine strains, one in the 5′‐noncoding region of the viral RNA, and one in capsid polypeptide VP3.

For many viruses, RNA is the holder of genetic information and serves as the template for both replication and translation. While host and viral proteins play important roles in viral decision‐making, the extent to which viral RNA (vRNA) actively participates in translation and replication might be surprising. Here, the focus is on flaviviruses, which include common human scourges such as dengue, West Nile, and Zika viruses, from an RNA‐centric viewpoint. In reviewing more recent findings, an attempt is (...) made to fill knowledge gaps and revisit some canonical views of vRNA structures involved in replication. In particular, alternative views are offered on the nature of the flaviviral promoter and genome cyclization, and the feasibility of refining in vitro‐derived models with modern RNA probing and sequencing methods is pointed out. By tracing vRNA structures from translation through encapsidation, a dynamic molecule closely involved in the self‐regulation of viral replication is revealed. (shrink)

High‐fidelity binding of transcription factors (TFs) to DNA target sites is fundamental for proper regulation of cellular processes, as well as for the maintenance of cell identity. Recognition of cognate binding motifs in the genome is attributed by and large to the DNA binding domains of TFs. As an additional mode of conferring binding specificity, noncoding RNAs (ncRNAs) have been proposed to assist associated TFs in finding their binding sites by interacting with either DNA or RNA in the vicinity of (...) their target loci. However, a well‐documented example of such a mechanism was lacking until we recently reported that a ncRNA made by Epstein‐Barr virus uses an RNA–RNA interaction with nascent transcripts generated from the viral genome to facilitate the recruitment of an interacting TF, PAX5, to viral DNA. This proof‐of‐principle finding suggests that cellular ncRNAs may likewise function in guiding interacting TFs to chromatin target sites. (shrink)

Viruses are essentially composed of a nucleic acid (segmented or not, DNA, or RNA) and a protein coat. Despite their simplicity, these small pathogens are responsible for significant economic and humanitarian losses that have had dramatic consequences in the course of human history. Since their discovery, scientists have developed different strategies to efficiently detect viruses, using all possible viral features. Viruses shape, proteins, and nucleic acid are used in viral detection. In this review, the development of these techniques, (...) especially for plant and mammalian viruses, their strengths and weaknesses as well as the latest cutting-edge technologies that may be playing important roles in the years to come are described. (shrink)

A hallmark of positive‐sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti‐microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune‐defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this (...) process remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole‐like structures of pathogens, thereby paving the way for the development of broadly effective anti‐microbial strategies for public health. (shrink)

The structures of spherical RNA plant tiruses, containing 180 copies of one protein subunit, are closely related to those of the animal RNA picornaviruses, which are built of 60 copies of each of three larger capsid proteins. Other spherical RNA and DNA viruses utilize the same structural motif as building units of the viral capsid. It is therefore probable that many of the simple RNA viruses, whether found in animals or plants, have had a common genetic origin. The original (...) gene may have coded for a protein that bound to specific molecules on the cell surface. (shrink)

Many viral and cellular mRNA species contain a leader sequence derived from a distant upstream site on the same gene by a process of RNA splicing. This process usually involves either nuclear functions or self‐splicing of RNA molecules. Coronavirus, a cytoplasmic RNA virus, unfolds yet another mechanism of joining RNA, which involves the use of a free leader RNA molecule. This molecule is synthesized and dissociates from the template RNA, and subsequently reassociates with the template RNA at down‐stream initiation (...) sites of subgenomic mRNAs to serve as the primer for transcription. This leader‐primed transcriptional process thus generates viral mRNAs with a fused leader sequence. A similar mechanism might also operate in the mRNA transcription of African trypanosomes. (shrink)

The discovery of a stable latent reservoir for HIV‐1 in resting memory CD4+ T cells provides a mechanism for lifelong persistence of HIV‐1. The long‐lived latently infected cells persist in spite of prolonged highly active antiretroviral therapy and present a major barrier to a cure of HIV‐1 infection. In this review, we discuss the current understanding of HIV‐1 persistence and latent viral infection in the context of effective antiretroviral therapy and the recent progress in purging latent viral reservoirs. (...) Recent studies demonstrate that reactivation of latent HIV‐1 is a promising strategy for the depletion of these viral reservoirs. A thorough evaluation of the anti‐latency activity of drug candidates should include the measurement of changes in intracellular viral RNA, plasma virus levels, and the size of latent viral reservoirs, as well as potential adverse effects. Currently, there are several technical barriers to the evaluation of anti‐latency drugs in vivo. We also discuss these challenging issues that remain unresolved. (shrink)

Positive transcription elongation factor b (P‐TEFb), which comprises cyclin‐dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P‐TEFb is required for productive elongation of transcription of protein‐coding genes by RNA polymerase II (pol II). In addition, P‐TEFb‐mediated phosphorylation of the carboxyl‐terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates (...) p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P‐TEFb could be effective anti‐viral agents. (shrink)

Throughout evolution, there has been interaction and exchange between RNA pools in the environment, and DNA and RNA pools of eukaryotic organisms. Metagenomic and metatranscriptomic sequencing of invertebrate hosts and their microbiota has revealed a rich evolutionary history of RNA virus shuttling between species. Horizontal transfer adapted the RNA pool for successful future interactions which lead to zoonotic transmission and detrimental RNA viral pandemics like SARS‐CoV2. In eukaryotes, noncoding RNA (ncRNA) is an established mechanism derived from prokaryotes to defend (...) against viral attack through innate immunity and regulation of host‐derived mRNA. Transgenerational inheritance of ncRNA is evidence for feedforward adaptive immunity and epigenetically encoded environmental change across generations, which may explain the ‘‘missing heritability’’ of common disease. Causal graph theory and the Price Equation can model epigenetic inheritance involving dynamic internal and external RNA pools. Experimental designs should include metatranscriptomic analyses to understand how ncRNA responds to rapidly changing environmental conditions, within and between organisms, and across generations. (shrink)

Here we discuss the hypothesis that the RNA components of the Ro ribonucleoproteins (RNPs), the Y RNAs, can be processed into microRNAs (miRNAs). Although Ro RNPs, whose main protein components Ro60 and La are targeted by the immune system in several autoimmune diseases, were discovered many years ago, their function is still poorly understood. Indeed, recent data show that miRNA-sized small RNAs can be generated from Y RNAs. This hypothesis leads also to a model in which Ro60 acts as a (...) modulator in the Y RNA-derived miRNA biogenesis pathway. The implications of these Y RNA-derived miRNAs, which may be specifically produced under pathological circumstances such as in autoimmunity or during viral infections, for the enigmatic function of Ro RNPs are discussed. (shrink)

The versatile clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has emerged as a promising technology for therapy and molecular diagnosis. It is especially suited for overcoming viral infections outbreaks, since their effective control relies on an efficient treatment, but also on a fast diagnosis to prevent disease dissemination. The CRISPR toolbox offers DNA‐ and RNA‐targeting nucleases that constitute dual weapons against viruses. They allow both the manipulation of viral and host genomes for therapeutic purposes and the detection (...) of viral nucleic acids in “Point of Care” sensor devices. Here, we thoroughly review recent advances in the use of the CRISPR/Cas system for the treatment and diagnosis of viral deleterious infections such as HIV or SARS‐CoV‐2, examining their strengths and limitations. We describe the main points to consider when designing CRISPR antiviral strategies and the scientific efforts to develop more sensitive CRISPR‐based viral detectors. Finally, we discuss future prospects to improve both applications. Also see the video abstract here: https://www.youtube.com/watch?v=C0z1dLpJWl4. (shrink)

ABSTRACT Why did the popping of the housing bubble bring the financial system—rather than just the housing sector of the economy—to its knees? The answer lies in two methods by which banks had evaded regulatory capital requirements. First, they had temporarily placed assets—such as securitized mortgages—in off‐balance‐sheet entities, so that they did not have to hold significant capital buffers against them. Second, the capital regulations also allowed banks to reduce the amount of capital they held against assets that remained on (...) their balance sheets—if those assets took the form of AAA‐rated tranches of securitized mortgages. Thus, by repackaging mortgages into mortgage‐backed securities, whether held on or off their balance sheets, banks reduced the amount of capital required against their loans, increasing their ability to make loans many‐fold. The principal effect of this regulatory arbitrage, however, was to concentrate the risk of mortgage defaults in the banks and render them insolvent when the housing bubble popped. (shrink)

The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration (...) of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation. (shrink)

Charles Eisenmann, dans un compte-rendu critique de la Pensée juridique, publié dans la Revue de droit public en 1961, écrivait : " On voudrait proclamer d'abord sans réserves, les rares qualités de l'ouvrage, qui en rendent la lecture très recommandable, en particulier pour ceux qui, jeunes ou juristes déjà formés, n'ont pas encore ou n'ont plus commerce très assidu avec la théorie ou la philosophie du droit. Ils prendront contact avec une pensée vivante et chaude, qui cherche avec ardeur, souplesse (...) et agilité." Les qualités qui ont conduit la Pensée juridique à être un des ouvrages de base de la formation théorique de toute une génération de juristes, celle des décennies 60-70, demeurent encore aujourd'hui intactes. C'est pourquoi il nous a paru souhaitable d'ouvrir la nouvelle collection des introuvables des éditions Panthéon- Assas par une réédition de l'ouvrage de Michel Virally. (shrink)

Within the sedimentation diagram of infective RNA preparations isolated from Tobacco Mosaic Virus, undegraded molecules form a sharp peak with a molecular weight corresponding to the total RNA content of the virus particle. Degradation kinetics by ribonuclease is of the linear, single-target type, indicating that the RNA is single-stranded. The intact RNA of a virus particle thus forms one big single-stranded molecule. Quantitative evaluation of the effect degradation by RNA-ase on the infectivity of the RNA shows that the integrity of (...) the entire molecule is required for its biological activity. (shrink)

Cowpea mosaic virus (CPMV) is the type member of the comovirus group, which contains 14 different plant viruses that have the same structural organization of genomic RNAs and virions and use the same mechanism for expression of the viral RNAs. The combined structure and organization of the two CPMV genomic RNAs is strikingly similar to that of the single genome of animal picornaviruses. This suggests a common ancestry and similar replication mechanisms. CPMV is by far the best‐studied comovirus and (...) we shall limit this review to some recent data on this virus. For additional general information the reader is referred to other recent reviews on CPMV and comoviruses1,2. (shrink)

Abstract The quasispecies theory is a helpful concept in the explanation of RNA virus evolution and behaviour, with a relevant impact on methods used to fight viral diseases. It has undergone some adaptations to integrate new empirical data, especially the non-deterministic nature of mutagenesis, and the variety of behavioural motifs in cooperation, competition, communication, innovation, integration, and exaptation. Also, the consortial structure of quasispecies with complementary roles of memory genomes of minority populations better fits the empirical data than did (...) the original concept of a master sequence and its mutant spectra. The high productivity of quasispecies variants generates unique sequences that never existed before and will never exist again. In the present essay, we underline that such sequences represent really new ontological entities, not just error copies of previous ones. Their primary unique property, the incredible variant production, is suggested here as quasispecies productivity, which replaces the error-replication narrative to better fit into a new relationship between mankind and living nature in the twenty-first century. (shrink)

During the 1960s, Howard M. Temin (1934-1994), dared to advocate a "heretical" hypothesis that appeared to be at variance with the central dogma of molecular biology, understood by many to imply that information transfer in nature occurred only from DNA to RNA. Temin's provirus hypothesis offered a simple explanation of both virus replication and viral-induced cancer and stated that Rous sarcoma virus, an RNA virus, is replicated via a DNA intermediate. Popular accounts of this scientific episode, written after the (...) discovery of an RNA-directed DNA polymerase in 1970, tend to describe the reaction to his proposition as ardent opposition. Typically these accounts use a 'molecular biology' standpoint emphasizing the central dogma's part in its rejection. In this article, however, this episode will be examined from a joint perspective of virology and experimental cancer research. From this perspective it is clear that Temin's work was well within the epistemological and methodological boundaries of virology and cancer research. Still, scientists did have reasons to doubt the provirus hypothesis, but these do not seem to be good enough to either justify an account that portrays Temin as a renegade or his ideas as heretical. (shrink)

Chromatin structure and dynamics regulate key cellular processes such as DNA replication, transcription, repair, remodeling, and gene expression, wherein different protein factors interact with the nucleosomes. In these events, DNA and RNA polymerases, chromatin remodeling enzymes and transcription factors interact with nucleosomes, either in a DNA‐sequence‐specific manner and/or by recognizing different structural features on the nucleosome. The molecular details of the recognition of a nucleosome by different viral proteins, remodeling enzymes, histone post‐translational modifiers, and RNA polymerase II, have been (...) explored in the recent past. The present review puts forth critical insights into the basic mechanisms of nucleosome recognition by the various protein factors and the role of distinct surface epitopes on a nucleosome. These determinants of the underlying specificity include features such as the acidic patch, arginine anchor, histone post‐translational modifications, core DNA, DNA lesions, and linker DNA. (shrink)

Animal, protist and viral messenger RNAs (mRNAs) are most prominently modified at the beginning by methylation of cap‐adjacent nucleotides at the 2′‐O‐position of the ribose (cOMe) by dedicated cap methyltransferases (CMTrs). If the first nucleotide of an mRNA is an adenosine, PCIF1 can methylate at the N6‐position (m6A), while internally the Mettl3/14 writer complex can methylate. These modifications are introduced co‐transcriptionally to affect many aspects of gene expression including localisation to synapses and local translation. Of particular interest, transcription start (...) sites of many genes are heterogeneous leading to sequence diversity at the beginning of mRNAs, which together with cOMe and m6Am could constitute an extensive novel layer of gene expression control. Given the role of cOMe and m6A in local gene expression at synapses and higher brain functions including learning and memory, such code could be implemented at the transcriptional level for lasting memories through local gene expression at synapses. (shrink)

Many enveloped viruses are released from infected cells by maturing and budding at the plasma membrane. During this process, viral core components are incorporated into membrane vesicles that contain viral transmembrane proteins, termed ‘spike’ proteins. For many years these spike proteins, which are required for infectivity, were believed to be incorporated into virions via a direct interaction between their cytoplasmic domains and viral core components. More recent evidence shows that, while such direct interactions drive budding of alphaviruses, (...) this may not be the case for negative strand RNA viruses and retroviruses. These viruses can bud particles in the absence of spike proteins, using only viral core components to drive the process. In some cases the spike proteins, without the viral core, can be released as virus‐like particles. Optimal budding and release may, therefore, depend on a ‘push‐and‐pull’ concerted action of core and spike, where oligomerization of both components plays a crucial role. (shrink)

The Sleeping Beauty transposon system is a nonviral DNA transfer tool capable of efficiently mediating transposition‐based, stable integration of DNA sequences of choice into eukaryotic genomes. Continuous refinements of the system, including the emergence of hyperactive transposase mutants and novel approaches in vectorology, greatly improve upon transposition efficiency rivaling viral‐vector‐based methods for stable gene insertion. Current developments, such as reversible transgenesis and proof‐of‐concept RNA‐guided transposition, further expand on possible applications in the future. In addition, innate advantages such as lack (...) of preferential integration into genes reduce insertional mutagenesis‐related safety concerns while comparably low manufacturing costs enable widespread implementation. Accordingly, the system is recognized as a powerful and versatile tool for genetic engineering and is playing a central role in an ever‐expanding number of gene and cell therapy clinical trials with the potential to become a key technology to meet the growing demand for advanced therapy medicinal products. (shrink)

All eukaryotic cellular mRNAs, and most viral mRNAs, are blocked at their 5′ ends with a cap structure (m7GpppX, where × is any nucleotide). Poliovirus, along with a small number of other animal and plant viral mRNAs, does not contain a 5′ cap structure. Since the cap structure functions to facilitate ribosome binding to mRNA, translation of poliovirus must proceed by a cap‐independent mechanism. Consistent with this, recent studies have shown that ribosomes can bind to an internal region (...) within the long 5′ noncoding sequence of poliovirus RNA. Possible mechanisms for cap‐independent translation are discussed. Cap‐independent translation of poliovirus RNA is of major importance to the mechanism of shut‐off of host protein synthesis after infection. Moreover, it is likely to play a role in determining poliovirus neurovirulence and attenuation. (shrink)

Retroviruses encode a small, basic nucleocapsid (NC) protein that is found complexed to genomic RNA within the viral particle. The NC protein appears to function not only in a histone‐like manner in packaging the RNA into the particle but also in specifically selecting the viral genomic RNA for packaging. A cysteine‐histidine (cys‐his) region, usually composed of 14 amino acids and reminiscent of the ‘zinc fingers’ of transcription factors, is the only highly conserved sequence element among the retroviral NC (...) proteins. This review discusses the biochemical properties of NC, and its possible role(s) in retroviral replication. We also speculate on how the biochemical properties may relate to its function in RNA recognition and packaging. (shrink)

Bromodomain‐containing 4 (BRD4), a member of Bromo and Extra‐Terminal (BET) family, recognizes acetylated histones and is of importance in transcription, replication, and DNA repair. It also binds non‐histone proteins, DNA and RNA, contributing to development, tissue growth, and various physiological processes. Additionally, BRD4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders. Inhibiting its functions with BET inhibitors (BETis) suppresses the progression of several types of cancer, creating an impetus for translating these (...) chemicals to the clinic. The diverse roles of BRD4 are largely dependent on its interaction partners in different contexts. In this review we discuss the molecular mechanisms of BRD4 with its interacting partners in physiology and pathology. Current development of BETis is also summarized. Further understanding the functions of BRD4 and its partners will facilitate resolving the liabilities of present BETis and accelerate their clinical translation. (shrink)

Natural genome editing from a biocommunicative perspective is the competent agent-driven generation and integration of meaningful nucleotide sequences into pre-existing genomic content arrangements, and the ability to (re-)combine and (re-)regulate them according to context-dependent (i.e. adaptational) purposes of the host organism. Natural genome editing integrates both natural editing of genetic code and epigenetic marking that determines genetic reading patterns. As agents that edit genetic code and epigenetically mark genomic structures, viral and subviral agents have been suggested because they may (...) be evolutionarily older than cellular life. This hypothesis that viruses and viral-like agents edit genetic code is developed according to three well investigated examples that represent key evolutionary inventions in which non-lytic viral swarms act symbiotically in a persistent lifestyle within cellular host genomes: origin of eukaryotic nucleus, adaptive immunity, placental mammals. Additionally an abundance of various RNA elements cooperate in a variety of steps and substeps as regulatory and catalytic units with multiple competencies to act on the genetic code. Most of these RNA agents such as transposons, retroposons and small non-coding RNAs act consortially and are remnants of persistent viral infections that now act as co-opted adaptations in cellular key processes. (shrink)

Current research on the origin of DNA and RNA, viruses, and mobile genetic elements prompts a re-evaluation of the origin and nature of genetic material as the driving force behind evolutionary novelty. While scholars used to think that novel features resulted from random genetic mutations of an individual’s specific genome, today we recognize the important role that acquired viruses and mobile genetic elements have played in introducing evolutionary novelty within the genomes of species. Viral infections and subviral RNAs can (...) enter the host genome and persist as genetic regulatory networks. Persistent viral infections are also important to understand the split between great apes and humans. Nearly all mammals and nonhuman primates rely on olfaction, i.e., chemoreception as the basis of the sense of smell for social recognition, group membership, and the coordination of organized social life. Humans, however, evolved other means to establish social bonding, because several infection waves by endogenous retroviruses caused a loss of odor receptors in human ancestors. The human independence from olfaction for social recognition was in turn one driver of the rather abrupt human transition to dependence on visual information, gesture production, and facial recognition that are at the roots of language-based communication. (shrink)

Viral modernity is a concept based upon the nature of viruses, the ancient and critical role they play in evolution and culture, and the basic application to understanding the role of information and forms of bioinformation in the social world. The concept draws a close association between viral biology on the one hand, and information science on the other – it is an illustration and prime example of bioinformationalism that brings together two of the most powerful forces that (...) now drive cultural evolution. The concept of viral modernity applies to viral technologies, codes and ecosystems in information, publishing, education and emerging knowledge systems. This paper traces the relationship between epidemics, quarantine, and public health management and outlines elements of viral-digital philosophy based on the fusion of living and technological systems. We discuss Covid-19 as a ‘bioinformationalist’ response that represents historically unprecedented level of sharing information from the sequencing of the genome to testing for a vaccination. Finally, we look at the US response to Covid-19 through the lens of infodemics and post-truth. The paper is followed by three open reviews, which further refine its conclusions as they relate to philosophy and the notion of the virus as Pharmakon. (shrink)

In this thought-provoking work, Tony D. Sampson presents a contagion theory fit for the age of networks. Unlike memes and microbial contagions, _Virality_ does not restrict itself to biological analogies and medical metaphors. It instead points toward a theory of contagious assemblages, events, and affects. For Sampson, contagion is not necessarily a positive or negative force of encounter; it is how society comes together and relates. Sampson argues that a biological knowledge of contagion has been universally distributed by way of (...) the rhetoric of fear used in the antivirus industry and other popular discourses surrounding network culture. This awareness is also detectable in concerns over _too much connectivity_, such as problems of global financial crisis and terrorism. Sampson’s “virality” is as established as that of the biological meme and microbe but is not understood through representational thinking expressed in metaphors and analogies. Rather, Sampson interprets contagion theory through the social relationalities first established in Gabriel Tarde’s microsociology and subsequently recognized in Gilles Deleuze’s ontological worldview. According to Sampson, the reliance on representational thinking to explain the social behavior of networking—including that engaged in by nonhumans such as computers—allows language to overcategorize and limit analysis by imposing identities, oppositions, and resemblances on contagious phenomena. It is the power of these categories that impinges on social and cultural domains. Assemblage theory, on the other hand, is all about relationality and encounter, helping us to understand the viral as a positively sociological event, building from the molecular outward, long before it becomes biological. (shrink)

The global response to managing the spread of HIV has recently undergone a significant shift with the advent of ‘treatment as prevention’, a strategy which presumes that scaling-up testing and treatment for people living with HIV will produce a broader preventative benefit. Treatment as prevention includes an array of diagnostic, technological and policy developments that are creating new understandings of how HIV circulates in bodies and spaces. Drawing on the work of Michel Foucault, we contextualize these developments by linking them (...) to systems of governance and discursive subjectivation. The goal of this article is to problematize the growing importance of viral suppression in the management of HIV and the use of related surveillance technologies. For people living with HIV, we demonstrate how treatment-as-prevention’s emphasis on individual and collective viral load is transforming the performative dimensions of embodied risk, affect, subjectivity and sex. (shrink)

This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the “degenerative” or the “retrograde (...) evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that (...) underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of rapid (...) scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (shrink)

Membranous organelles allow sub‐compartmentalization of biological processes. However, additional subcellular structures create dynamic reaction spaces without the need for membranes. Such membrane‐less organelles (MLOs) are physiologically relevant and impact development, gene expression regulation, and cellular stress responses. The phenomenon resulting in the formation of MLOs is called liquid–liquid phase separation (LLPS), and is primarily governed by the interactions of multi‐domain proteins or proteins harboring intrinsically disordered regions as well as RNA‐binding domains. Although the presence of RNAs affects the formation and (...) dissolution of MLOs, it remains unclear how the properties of RNAs exactly contribute to these effects. Here, the authors review this emerging field, and explore how particular RNA properties can affect LLPS and the behavior of MLOs. It is suggested that post‐transcriptional RNA modification systems could be contributors for dynamically modulating the assembly and dissolution of MLOs. (shrink)

In late March of 2020, a new hashtag, #FilmYourHospital, made its first appearance on social media. The hashtag encouraged people to visit local hospitals to take pictures and videos of empty hospitals to help “prove” that the COVID-19 pandemic is an elaborate hoax. Using techniques from Social Network Analysis, this case study examines how this conspiracy theory propagated on Twitter and whether the hashtag virality was aided by the use of automation or coordination among Twitter users. We found that while (...) much of the content came from users with limited reach, the oxygen that fueled this conspiracy in its early days came from a handful of prominent conservative politicians and far right political activists on Twitter. These power users used this hashtag to build awareness about the campaign and to encourage their followers to break quarantine and film what is happening at their local hospitals. After the initial boost by a few prominent accounts, the campaign was mostly sustained by pro-Trump accounts, followed by a secondary wave of propagation outside the U.S. The rise of the #FilmYourHospital conspiracy from a single tweet demonstrates the ongoing challenge of addressing false, viral information during the COVID-19 pandemic. While the spread of misinformation can be potentially mitigated by fact-checking and directing people to credible sources of information from public health agencies, false and misleading claims that are driven by politics and supported by strong convictions and not science are much harder to root out. (shrink)

There is an ecology of bad ideas, just as there is an ecology of weeds, and it is characteristic of the system that basic error propagates itself.–Gregory Bateson, Steps Towards an Ecology of Mind...

Changes in the abundance of protein and RNA molecules can impair the formation of complexes in the cell leading to toxicity and death. Here we exploit the information contained in protein, RNA and DNA interaction networks to provide a comprehensive view of the regulation layers controlling the concentration‐dependent formation of assemblies in the cell. We present the emerging concept that RNAs can act as scaffolds to promote the formation ribonucleoprotein complexes and coordinate the post‐transcriptional layer of gene regulation. We describe (...) the structural and interaction network properties that characterize the ability of protein and RNA molecules to interact and phase separate in liquid‐like compartments. Finally, we show that presence of structurally disordered regions in proteins correlate with the propensity to undergo liquid‐to‐solid phase transitions and cause human diseases. Also see the video abstract here https://youtu.be/kfpqibsNfS0. (shrink)

Viruses are major drivers of global biogeochemistry and the etiological agents of many diseases. They are also the winners in the game of life: there are more viruses on the planet than cellular organisms and they encode most of the genetic diversity on the planet. In fact, it is reasonable to view life as a viral incubator. Nevertheless, most ecological and evolutionary theories were developed, and continue to be developed, without considering the virosphere. This means these theories need to (...) be to reinterpreted in light of viral knowledge or we need to develop new theory from the viral point-of-view. Here we briefly introduce our viral planet and then address a major outstanding question in biology: why is most of life viral? A key insight is that during an infection cycle the original virus is completely broken down and only the associated information is passed on to the next generation. This is different for cellular organisms, which must pass on some physical part of themselves from generation to generation. Based on this premise, it is proposed that the thermodynamic consequences of physical information (e.g., Landauer’s principle) are observed in natural viral populations. This link between physical and genetic information is then used to develop the Viral Information Hypothesis, which states that genetic information replicates itself to the detriment of system energy efficiency (i.e., is viral in nature). Finally, we show how viral information can be tested, and illustrate how this novel view can explain existing ecological and evolutionary theories from more fundamental principles. (shrink)

As companies increasingly communicate CSR initiatives through social media, viral message propagation has become a crucial prerequisite for CSR success. Evidence from two experimental studies, one based on a national representative online sample, shows that social media peers’ endorsement of a CSR message in terms of number of shares, likes and positive replies contributes to an individual’s intention to share it on the social network and thereby participate in message propagation, and that this process can be explained by normative (...) influences exerted by the social media community through the activation of injunctive and descriptive norms, as well as social identity motives. Findings further confirmed that the norm-activating effects of social media endorsement are moderated by the empowering qualities of the CSR message, the sharing source of the message by affecting CSR credibility, and the recipient’s interdependent self-construal. Corporate communication managers are advised to achieve a high degree of initial social media endorsement of their CSR message, for recipients of the message to perceive social pressure motivating message sharing with their social media peers. (shrink)