Epistemic_Statements  

CORD-19:113f9670b9a495a6352bc03bf2d923e60fa41b7d JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 993-1201 Epistemic_statement denotes However, the dynamic interplay between hosts and viruses in nature ( Figure 1 ) is difficult to recapitulate in laboratory-based studies that employ a single viral clone infecting an isogenic host population.
T2 1334-1488 Epistemic_statement denotes In this process, genetic differences between these species, not genetic similarities, are what dictate the evolutionary adaptations required by the virus.
T3 1615-1808 Epistemic_statement denotes Therefore, the results of experiments using clonal hosts and clonal viruses in the laboratory may not always reveal the spectrum of possible host-virus interactions that truly exists in nature.
T4 1809-2018 Epistemic_statement denotes Third, in studies of viruses infecting their natural host species, including cell lines derived from those species, host defense mechanisms can be masked because the viruses have already evolved to evade them.
T5 2019-2157 Epistemic_statement denotes In all of these instances, experiments conducted in non-host species (referred to here as heterologous species) can be highly informative.
T6 2158-2390 Epistemic_statement denotes Here we consider both the strengths and limitations of approaches involving infections of heterologous animals, heterologous cell lines, and even cell lines differing only by the expression of single genes from heterologous species.
T7 3367-3539 Epistemic_statement denotes Notably, the identification of the TRIM5α restriction factor instead resulted from comparing cell lines derived from susceptible and resistant primate species (Figure 2A ).
T8 4586-4771 Epistemic_statement denotes It is important to recognize that this potent anti-retroviral gene is constitutively expressed in many human cell types, yet lies silent because HIV has evolved to escape its detection.
T9 4772-4937 Epistemic_statement denotes The powerful antiviral activity of TRIM5α was only revealed when HIV was paired with cells of a heterologous host species to which the virus is not yet well adapted.
T10 4938-5152 Epistemic_statement denotes Removing HIV from the context of the human genetic landscape uncovered how exquisitely vulnerable HIV is to naturally existing host factors that may ultimately prove vital to eradicating this deadly human pathogen.
T11 5535-5657 Epistemic_statement denotes This potentially contributes to the narrow host range of influenza B viruses, which have only been found to infect humans.
T12 6749-6922 Epistemic_statement denotes These cell lines may be derived from species other than the one from which the virus was isolated or from tissues other than the ones in which the virus normally replicates.
T13 7125-7352 Epistemic_statement denotes It is important to consider that, by ignoring other less permissive cell lines, we may be casting aside opportunities to discover new restriction factors and other cellular factors of importance to particular viral life cycles.
T14 8469-8614 Epistemic_statement denotes The acquired point mutations may also reflect adaptations specific to the innate immune defenses of chickens, but this has not been demonstrated.
T15 8615-8778 Epistemic_statement denotes The growing field of experimental evolution has the potential to help us understand the adaptive processes that viruses undergo when they acclimate to novel hosts.
T16 9726-9903 Epistemic_statement denotes The authors of these studies proposed that constant evolutionary struggle between viral antagonists and host defenses uniquely shaped these interactions in each primate species.
T17 10125-10250 Epistemic_statement denotes Therefore, a cross-species viewpoint can help reveal key functional differences in how viruses adapt to defeat host immunity.
T18 10479-10604 Epistemic_statement denotes Cross-species infections of live animals in laboratory settings can be useful for understanding virus evolution in new hosts.
T19 11031-11258 Epistemic_statement denotes H5N1 does not yet transmit efficiently from human to human via aerosolization and respiratory inhalation, which is taken to mean that the virus requires additional mutational changes before epidemic spread in humans can result.
T20 11259-11464 Epistemic_statement denotes In line with this hypothesis, three recent studies identified small combinations of viral mutations that result in respiratory transmission of this virus between ferrets in neighboring cages [40, 44, 45] .
T21 11654-11792 Epistemic_statement denotes However, this work illustrates how crossspecies infections of animals may reveal exactly how viruses adapt to new hosts, including humans.
T22 11793-11894 Epistemic_statement denotes The implications of intra-species genetic diversity can also be studied with experimental approaches.
T23 12432-12595 Epistemic_statement denotes This experiment nicely illustrates a central tenet of the Red Queen hypothesis [49] , namely that unique host genotypes exert unique selective pressure on viruses.
T24 12596-12827 Epistemic_statement denotes The same concept has also been demonstrated in primates, where retroviruses have been shown to take specific and reproducible evolutionary trajectories depending on the particular restriction factor alleles of their host [23, 26] .
T25 13107-13309 Epistemic_statement denotes Further studies exploiting genetic differences between closely related strains and species holds great promise for revealing the fundamental rules that govern co-evolution in host and virus populations.
T26 13310-13382 Epistemic_statement denotes Virus evolution during host switching can also be monitored in the wild.
T27 13383-13576 Epistemic_statement denotes An interesting and often-cited case involves the repeated release of the myxoma poxvirus in Europe and Australia as a form of biological control over invasive European rabbit populations [50] .
T28 13709-13826 Epistemic_statement denotes However, after release into European rabbit populations, the emergence of less virulent viral forms quickly followed.
T29 13827-13989 Epistemic_statement denotes Attenuation of viral pathogenicity resulted in increased rabbit survival times, which may have optimized viral transmission to new rabbits through insect vectors.
T30 14130-14263 Epistemic_statement denotes While this is as an illustrious example of host-virus co-evolution, the mutations underlying adaptation have not yet been identified.
T31 14264-14531 Epistemic_statement denotes It will be challenging to determine which specific mutational changes conveyed the observed fitness improvements, as a majority of the mutations that accumulated in host and virus genomes are predicted to have been evolutionarily neutral or even slightly deleterious.
T32 14532-14754 Epistemic_statement denotes This limitation pertains to most experiments that involve sampling from infection dynamics unfolding in nature, and can be especially vexing in highly heterogeneous virus populations and for protocols with sparse sampling.
T33 15010-15209 Epistemic_statement denotes Future studies may reveal the molecular details of the cross-species transmission of myxoma virus and the host-virus genetic conflict that unfolded in the context of this ecologically complex system.
T34 15459-15720 Epistemic_statement denotes In turn, mechanistic studies of host-virus interactions benefit from this evolution-based perspective, as observations of positive selection and species-specific mutational patterns can be used to guide the functional dissection of host-virus interactions [9] .
T35 15866-16112 Epistemic_statement denotes In order to enhance the power of this approach, it will be important to curate panels of cell lines from species that constitute viral reservoirs in nature, as well as from species that may serve as new or intermediate hosts for emerging disease.
T36 16113-16372 Epistemic_statement denotes By extending the model organisms paradigm with a cross-species view of virology, which incorporates the vast genetic diversity driving the dynamics of host-virus interactions, we may be poised to gain the upper-hand in these continuing struggles for survival.
T37 16373-16551 Epistemic_statement denotes • Dynamic aspects of virology often aren't well suited to traditional model system approaches • Many viruses are well adapted to their natural hosts, masking pathways of immunity
T38 16552-16620 Epistemic_statement denotes • Cross-species infections yield unique insight into innate immunity
T39 16621-16698 Epistemic_statement denotes • Viral adaptation can be effectively studied in novel host cells and species
T40 16699-16754 Epistemic_statement denotes Different types of virus-host dynamics are illustrated.
T41 16908-16998 Epistemic_statement denotes Not shown are additional genetic differences that exist within host and viral populations.
T42 16999-17225 Epistemic_statement denotes All of these genetic differences have the potential to contribute to viral host range, which may be broad or narrow (colored triangles), and may make some viruses more likely to evolve to expand their host range (dotted line).
T43 17226-17403 Epistemic_statement denotes This dynamic interplay between hosts and viruses is difficult to recapitulate in laboratory-based studies that employ a single viral clone infecting an isogenic host population.
T44 17404-17642 Epistemic_statement denotes In cases where resistance is conveyed by a dominant genetic factor, as would be the case with a cellular restriction factor or other immunity protein, the genetic basis for resistance can be uncovered by performing the illustrated screen.
T45 17891-18051 Epistemic_statement denotes B) Once cellular immunity proteins have been identified, heterologous gene studies can also be used to finely map the genetic determinants of viral recognition.
T46 18529-18707 Epistemic_statement denotes By comparing unique mutations in the resistant (red) versus susceptible (blue and green) orthologs, the genetic determinants of viral detection can be identified (orange arrows).
T47 18708-18950 Epistemic_statement denotes Of these, the best candidate protein regions or residues (dark orange arrows) will be those with signatures of positive selection over the evolution of these species (bottom right, positions under positive selection indicated with asterisks).
T48 19463-19687 Epistemic_statement denotes In cases where incompatibility is observed between a virus and a cell line of a heterologous species, this presents an opportunity to identify cellular barriers to infection in a genetically tractable system (see Figure 2 ).
T49 19926-20034 Epistemic_statement denotes Also, in such systems viral evolution experiments elucidate how a virus can escape specific cellular blocks.
T50 20097-20209 Epistemic_statement denotes This diagram illustrates the steps by which a virus is transmitted from its original host to a new host species.
T51 20210-20403 Epistemic_statement denotes While all organisms are continuously exposed to the viruses of other species, infection resulting in virus replication and potentially illness (step 1) is thought to be a relatively rare event.
T52 20528-20644 Epistemic_statement denotes Of these, only some will progress to the point of epidemic or pandemic spread through the new host species (step 3).
T53 20645-20917 Epistemic_statement denotes In theory, each of these steps may or may not require the acquisition of novel mutations in the viral genome, although existing evidence suggests that additional mutations usually do accumulate in viral genomes as viruses become more and more adapted to a particular host.
T54 20918-21026 Epistemic_statement denotes Virus mutations can be acquired through point mutation, insertion, deletion, recombination, or reassortment.
T55 21027-21132 Epistemic_statement denotes The acquisition of combinations of mutations may be required for viruses to advance through this process.