Viruses Quotes

“The accelerating pace of zoonotic transmission of novel viruses into humans is attributable to anthropogenic epidemiologic factors. Only behavior modification or medical management of this future health burden will minimize the risks of future zoonoses for human populations.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“The trends speak to an unavoidable truth. Society's future will be challenged by zoonotic viruses, a quite natural prediction, not least because humanity is a potent agent of change, which is the essential fuel of evolution. Notwithstanding these assertions, I began with the intention of leaving the reader with a broader appreciation of viruses: they are not simply life's pathogens. They are life's obligate partners and a formidable force in nature on our planet. As you contemplate the ocean under a setting sun, consider the multitude of virus particles in each milliliter of seawater: flying over wilderness forestry, consider the collective viromes of its living inhabitants. The stunnig number and diversity of viruses in our environment should engender in us greater awe that we are safe among these multitudes than fear that they will harm us.

Personalized medicine will soon become a reality and medical practice will routinely catalogue and weigh a patient's genome sequence. Not long thereafter one might expect this data to be joined by the patient's viral and bacterial metagenomes: the patient's collective genetic identity will be recorded in one printout. We will doubtless discover some of our viral passengers are harmful to our health, while others are protective. But the appreciation of viruses that I hope you have gained from these pages is not about an exercise in accounting. The balancing of benefit versus threat to humanity is a fruitless task. The viral metagenome will contain new and useful gene functionalities for biomedicine: viruses may become essential biomedical tools and phages will continue to optimize may also accelerate the development of antibiotic drug resistance in the post-antibiotic era and emerging viruses may threaten our complacency and challenge our society economically and socially. Simply comparing these pros and cons, however, does not do justice to viruses and acknowledge their rightful place in nature.

Life and viruses are inseparable. Viruses are life's complement, sometimes dangerous but always beautiful in design. All autonomous self-sustaining replicating systems that generate their own energy will foster parasites. Viruses are the inescapable by-products of life's success on the planet. We owe our own evolution to them; the fossils of many are recognizable in ERVs and EVEs that were certainly powerful influences in the evolution of our ancestors. Like viruses and prokaryotes, we are also a patchwork of genes, acquired by inheritance and horizontal gene transfer during our evolution from the primitive RNA-based world.

It is a common saying that 'beauty is in the eye of the beholder.' It is a natural response to a visual queue: a sunset, the drape of a designer dress, or the pattern of a silk tie, but it can also be found in a line of poetry, a particularly effective kitchen implement, or even the ruthless efficiency of a firearm. The latter are uniquely human acknowledgments of beauty in design. It is humanity that allows us to recognize the beauty in the evolutionary design of viruses. They are unique products of evolution, the inevitable consequence of life, infectious egotistical genetic information that taps into life and the laws of nature to fuel evolutionary invention.”
― Michael G. Cordingley, Viruses: Agents of Evolutionary Invention

“The basis for the potential of all virolytic therapeutics resides in the exquisite selectivity they exhibit for infecting and killing cancer cells. The very nature of cancer cells makes them extremely susceptible to virus infection: they divide in an uncontrolled fashion and are metabolically hyperactive, thus they exhibit greatly diminished capacity for apoptosis and innate immune defense against virus infection. While normal cells reduce metabolic activity, activate apoptotic signaling pathways, and block cell cycle progression in response to virus infection, cancer cells remain oblivious. These are perfect conditions for the growth of viruses, particularly those that are attenuated for growth in normal cells. Consequently, oncolytic viruses are specific reagents that target cancer cells and spread from cell to cell within tumors. It has become apparent that the direct lytic effects of viruses on cancer cells is just one element of their therapeutic effects, the cytolisis of infected cells releases viral and cellular antigens that can provoke anti-tumor immune responses, and some cancer therapeutic viruses are engineered to deliver additional genes such as immune activators to augment these effects.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“Vaccination with a live-attenuated virus vaccine can be compared with the cross-species transmission of viruses that cause zoonotic infection. If the vaccine strain is an RNA virus, it can be expected that the vaccine inoculum will be made up of a population of genotypes representing the quasispecies which is created during replication and amplification of the virus in host cells. Furthermore, virus replication in the vaccine recipient creates genetic diversity, providing an opportunity for reversion of the attenuated phenotype. This is a real but rarely realized disadvantage of live-attenuated virus vaccines.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“ERV envelope genes possess unique properties that make them suitable for use in forming the placenta: they are fusogenic proteins and they have immunosuppresive properties. Eutherian (placental) mammals distinguish themselves from nonplacental animals in the ability of the female to nurture the fertilized ovum and growing embryo within the body. The placenta is a transient tissue of embryonic origin whose evolution made it unnecessary to partition the embryo into a protective egg, which matured outside the mother's body. It serves two purposes for the maturing embryo: it is a conduit for respiratory gasses and nourishment supplied by the mother, and it provides an environment of immune tolerance. The fetus is necessarily half-foreign tissue, an allograft within the mother. It draws half of its genetic, and hence antigenic, identity from maternal and half from paternal genes. If the fetus is to mature within the mother, it must be isolated from the maternal immune system such that a graft-versus-host response does not reject it. The placenta forms early after implantation of the embryo. Syncytins mediate the formation of a continuous fused layer of cells around the embryo, isolating it from the mother, yet allowing essential nutrients to traverse from the mother's system. Although the observations on human syncytin-1 and -2 were compelling, it was left to scientists to definitively link syncytins to placental formation by studying mice. Here two syncytins (dubbed A and B) from murine ERVs were implicated, and genetic experiments with mice defective in these genes confirmed that their dysfunction disrupted placental formation. Notably, however, syncytin-A and -B were not syntenic with the human syncytins. That is, the human and mouse genes are not descended fron common ancestral syncytins; they have arisen by separate ERV gene capture events from different families of ERV in human and mouse ancestors.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“In early primates, we can pinpoint a particular ERV integration event into the locus of the pancreatic amylase gene that conferred upon our ancestors the ability to express their amylase genes in the salivary gland. This heritable change provided for tissue-specific expression of the gene and gave us our sweet tooth. Here, the introduction of new gene regulatory DNA sequences close to the transcriptional start site of the amylase gene allowed salivary secretion of amylase. The resulting phenotype must have offered advantages to primates as they developed a diet containing more complex carbohydrates.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“The litter of ERVs across vertebrate genomes, mainly in the form of defective and deleted proviruses, mutationally inactivated proteins coding sequences, and isolated LTRs, confirms that the vast majority of endogenized retroviral genones decay to nonfunctional sequences. If they have been silenced by cellular regulatory mechanisms or if their gene products are not under purifying or positive selective pressures, their DNA sequences will be under no selective pressure to retain their functionality. Over time, they accumulate random mutations and their sequences drift without consequence to the host. That ERVs mostly become such inconsequential DNA is a topic of hot debate; it is, however, an easy matter to pick several examples that illustrate how hosts can benefit from their ERVs. As for all matters of evolution, we bear witness only to the successful events that are now fixed in genomes. Evolutionary failures, no matter they far outnumber the successes, go unrecorded, rapidly purged from the gene pool.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“Collectively, the veritable zoo of mobile genetic elements comprises a remarkable 40 percent of our genome. The retroviral sequences littered across all vertebrate genomes are termed endogenous retroviral elements (ERVs). Endogenous retroviral sequences themselves are so plentiful that they take up more space in our genomes than genes encoding human proteins. Their existence is evidence of waves of retroviral infection and germline infiltration throughout vertebrate evolution. We have only recently begun to realize the powerful influence that retroviruses wielded over the evolution of vertebrate genomes and the identity of our species. They were catalysts of genetic instability that fueled evolutionary change; today they are vestiges of their former selves, fossils of viruses that once preyed on vertebrate hosts. Their remains are evidence of pyrrhic victories of sorts in many wars and arms races that have taken place between retroviruses and hosts. Most endogenous retroviruses have long been silenced by host cell restriction mechanisms. Associated with no phenotype, and under no selective pressure they become nonviable after millions of years of mutational drift, resulting in the accumulation of mutations and deletions in their coding sequences and control elements.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“The researchers looked deeper into these observations, in hopes of gaining insight into the mechanisms underlying the high evolutionary rate and extraordinary immunologic plasticity of influenza HA. They probed in more detail the precise codons that are used by the virus to encode the influenza HA1 protein. The discriminated between codons on the basis of volatility. Each three-nucleotide codon is related by a single nucleotide change to nine 'mutational neighbours.' Of those nine mutations, some proportion change the codon to a synonymous codon and some change it to a nonsynonymous one, which directs the incorporation of a different amino acid into the protein. More volatile codons are those for which a larger proportion of those nine mutational neighbours encode an amino acid change. The use of particular codons in a gene at a frequency that is disproportionate to their random selection for encoding a chosen amino acid is termed codon bias. Such bias is common and is influenced by many factors, but here the collaborators found strong evidence for codon bias that was particular for and restricted to the amino acids making up the HA1 epitopes. Remarkably, they observed that influenza employs a disproportionate number of volatile codons in its epitope-coding sequences. There was a bias for the use of codons that had the fewest synonymous mutational neighbours. In other words, influenza HA1 appears to have optimized the speed with which it can change amino acids in its epitopes. Amino acid changes can arise from fewer mutational events. The antibody combining regions are optimized to use codons that have a greater likelihood to undergo nonsynonymous single nucleotide substitutions : they are optimized for rapid evolution.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“Such then is the nature of quasispecies : the density of the sequence cloud at any point in sequence space is determined by the relative fitness of the sequence; regions of the cloud representing sequences of lesser fitness will be less densely populated and those with higher fitness, most populated. Here lies the most powerful quality of viral quasispecies: the density distribution of fitness variants dictates that sequences are represented at frequencies in relation to their relative fitness. Genomes with lower fitness will replicate poorly, or not at all, and the fittest genomes will replicate most efficiently. It therefore follows that there is a large bias toward the production of well-adapted genotypes: there are more of them, and they undergo most replicative cycles. This can permit viruses to experience evolutionary adaptation at rates that are orders of magnitude higher than those that could be achieved by truly random unbiased mutation. Sequences rapidly condense around the fittest area of the sequence space. Should the environment change, and, therefore, selective pressures change, a quasispecies can opportunistically exploits its inherent adaptive potential. Genotypes rapidly and ever-faster gravitate toward the cloud's new notational center of gravity. Changes in the fitness landscape of the sequence space that is occupied by a quasispecies are the natural consequence of altered selective pressures operating on the virus population. Such alterations may be the consequence of changed immunologic pressures exerted by the host, the application of antiviral drug therapy, or even cross-species transmission requiring the virus to adapt to a new host. Genotypes that once occupied the 'central' space, reserved for the fittest genotypes, are reduced in frequency and now occupy the more sparsely populated fringes of the fitness landscape; the very edge of the sequence cloud if you will. Here too lies an advantage for a quasispecies: it has a memory. The once best-adapted genotypes, now at a fitness disadvantage, can persist in the quasispecies as minor sequence variants. Under circumstances of fluctuating selective pressures, the ability of the population to recall an 'old' genome variant is a great asset. The quasispecies can rapidly respond and adapt by plucking out a preexisting variant and quickly coalescing around it to recreate an optimal fitness landscape.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“Unlike lytic phages, CTXφ can actively replicate within V. cholerae and generate progeny phages without killing its host cell. The process of phage induction for CTXφ is also different; it occurs without excision of the prophage from the host cell chromosome. Consequently, the CTXφ lysogen can be induced to enter its replicative cycle and release progeny phage particles while preserving both the cell host and the prophage. CTXφ can, therefore, pursue lysogeny, being replicated as part of the bacterial genome as well as productive infection and release of progeny phage. It can thus simultaneously be propagated vertically and horizontally between host cells. It can have its cake and eat it too.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention

“It is also reasonable to speculate that the capacity of prophages to be induced at a low frequency must in itself be advantageous to the phage genome. It is attractive to think of this as a hedging strategy, in which the genetically identical phage population can simultaneously exploit two different phenotypes - in this case, to optimize its probability of genetic success. Lysogeny can be considered as phage conservatism, a strategy suited to survival in adverse conditions, Lytic replication is high-stakes gambling that pays off with confident prediction of outcomes. A phage that never takes advantage of the rewards of the high-stakes game (except under dire and uncertain circumstances) will not be as evolutionary successful as the generally conservative phage with an occasionally successful flutter that, rewards with a burst of more rapid amplification. It seems likely then that phages have evolved to spontaneously induce, in a stochastic manner, in order to take advantage of lytic replication while not jeopardizing the genetically identical population of prophages still languishing in the chromosones of their slowly dividing hosts.”
― Michael G Cordingley, Viruses: Agents of Evolutionary Invention