4000302260center8/17/2018 3300095000 8/17/2018 left308610000 Viruses

May 3, 2019 0 Comment




Viruses: Friends or Foes?
Name: Jeanine Kaitlin Subramoney
Student no: 216046281
Contents Page
Contents Page number
Introduction 2
Main Text: 3-13
Symbiosis and Mutagenesis
Manipulated for modern technology
Allow for evolution
Research for cancer cells
Mammalian Health
Bacteriophages and their impact on human health 3-4
Conclusion 13-14
References 14-17
Viruses are intracellular obligate parasites that lack the genetic information essential for protein synthesis, mainly ribosomes. The plethora of studies on viruses are associated with diseases and their antagonistic roles in society, emphasizing their roles as pathogens and overlooking their environmental roles in the symbiosis continuum of life and the mutualistic relationships amongst viruses and hosts.
Viruses play an important role in human health, not only by controlling human populations and shaping evolution but by their consistent appearance in the human genome, suggesting that they serve as more mutualistic and imperative rather than antagonistic. The human amylase gene is one example which allows for the consumption of novel foods and was only mutated due to the presence of retroviruses in the genome.

The prevalence and abundance of viruses in certain societies have been used as indicators of origin of distinct viruses and diseases amongst populations. This role is extremely important, as the use of a virus can pinpoint the source of a disease and allow for prevention and therapy treatments to be obtained or optimized.

The adaptation and presence of the endogenized env gene forms the precursor of the syncytin gene in mammals, a significant gene required in the formation of the placenta, an essential organ whose main function is the formation of fetal-maternal interface that provides support for the developing embryo by mediating metabolic exchanges (Esnault et al., 2013).

Manipulation of viruses for modern technology allows for vaccines that are innovative towards HIV/ AIDS as well as cancer. The study of oncology and the therapeutic applications of viruses serve to highlight the various modes of actions of viruses, their ability to recombinase and change our approaches towards medicine.

Additionally, viruses can be used to enhance nanoscience and the creation of novel batteries using viruses in one of the promising applications of viruses. New research has designated the use of recombinant M13 phage particles as organic templates to polymerize nanowires that serve as building blocks for semiconductors or magnetic materials (Roossinck, 2015).

Lastly, insecticidal application of viruses e.g. Baculovirus, and the Avipoxvirus seeks to highlight that the symbiosis of a virus is dependant on the type of environment it is exposed to and that under the correct conditions the possibilities of viruses are endless.

This report seeks to highlight and emphasize the various benefits and applications of viruses in society, ecology, and evolution and mammalian health.

Main Text
Viruses play a role in mutagenesis and symbiosis
Symbiotic relationships can shape the evolution of organisms present in an environment, and placing viruses in this perspective provides a framework for understanding virus-host relationships and viral ecology. Since viruses must create an intimate relationship with their hosts or vectors in order to infect, replicate and propagate they can be considered symbionts with their hosts due to their evolutionary plasticity and used as excellent models for understanding the development and maintenance of symbiotic relationships (Roossinck and Baz´an, 2017).

Symbiosis encompasses varied lifestyles, including antagonistic or pathogenic, commensal, and mutualistic. Though antagonistic relationships lead to coevolution, this is not always clear in virus-host interactions, and impacts on evolution may be complex (Roossinck and Baz´an, 2017). Commensalism implies a hitchhiking role for viruses—sel?sh elements just along for the ride (Roossinck and Baz´an, 2017). Mutualistic relationships are the most well studied and they reveal the importance of viruses when considering host ecology. Ultimately, symbiosis can lead to symbiogenesis, or speciation through fusion, and the presence of large amounts of viral sequence in the genomes of everything from bacteria to humans, including some important functional genes, illustrates the signi?cance of viral symbiogenesis in the evolution of all life on Earth (Roossinck and Baz´an, 2017).

The synthesis of bacterial biofilms is mainly due to phages. In dense viral populations, they could serve as a reservoir of nutrients. For example, in nutrient-poor environments such as coral reefs, viruses are acquired and digested by marine sponges (Roossinck and Baz´an, 2017).
Furthermore, phages contain essential functions for microbes, such as toxin production that allow them to invade their macro hosts and horizontal gene transfer of essential elements (Mai-Prochnow, et al., 2015). Harboring viruses allows bacteria to kill their competitors thus protecting themselves and their hosts, allowing for colonization of new niches. Another effective method is the conversion of a few cells in the population to a lytic state, creating viruses that kill non-lysogenic competitors.

Viruses of other eukaryotic microbes have positive effects on growth, fertility, or persistence of their hosts. An example of this is the killer virus in yeast which provides an intriguing system of protection for the host. The virus produces a toxin in an inactive form that is released into the environment and readily taken up by other yeast. The activation of the toxin occurs by processing after uptake. However, in yeast cells harboring the virus, the presence of the inactive toxin moves all forms of the toxin into the ubiquitin degradation pathway, preventing the killer effect (Schmitt and Breinig, 2006.).

In addition, viruses play an essential role in the survival of microbes in their natural environment. At the Yellowstone National Park, plants that can survive in geothermal areas tolerate the high soil temperatures only when they are colonized by a fungus that is, sequentially, infected with a virus (Márquez and Roossinck, 2012). Viruses can also help plants with abiotic stresses, studies of acute viruses conferred drought tolerance to plants, and that the cucumber mosaic virus could confer cold tolerance (Xu et al., 2008). The mechanism for drought tolerance imparted by the cucumber mosaic virus was recently shown to involve RNA silencing (Xu et al., 2008), elevated levels of various metabolites and many other unidentified factors that may be involved.

Plant infections additionally affect biotic pressure factors. In white clover, contamination with the White clover mosaic, infections makes the plants less alluring to contagious gnats. Zucchini yellow mosaic infection taints wild gourds and diminishes the generation the production of volatile compounds that attract beetles to the plants The creepy crawlies are vectors of a bacterial wither pathogen, so the infection lessens transmission of the shrivel microorganisms (Shapiro et al., 2013). Plants are regularly tainted with asymptomatic determined infections that vary to some degree from tireless infections in different frameworks. These infections are vertically transmitted at about 100% rates; no horizontal gene transfer has been illustrated (Roossinck, 2012). They stay with their hosts for extended stretches of time, maybe a huge number of years. White clover cryptic virus a persistent virus ubiquitous in white clover suppresses the formation of nitrogen-fixing nodules when adequate nitrogen is present in the soil (Nakatsukasa-Akune et al., 2005), sparing the plant from delivering an expensive organ when it isn’t required. The science of most other importunate plant infections remain unknown, yet such long affiliations and large amounts of vertical transmission suggest beneficial connections.

Manipulated for modern technology
Baculoviruses, are pathogenic in nature, infecting insects and arthropods by coding for genes needed for viral establishment and reproduction and their viral genetic material is protected by a protein coat termed, polyhedron. Most insect baculoviruses must be eaten by the host, typically fatal, to produce an infection.

These viruses serve as excellent mechanisms for species-specific and narrow field insecticidal applications. They have been shown to have no negative impacts on plants, mammals, birds, and fish and on non-target insects. This is particularly desirable for the conservation of beneficial insects or when an ecologically sensitive area is being treated. Furthermore, baculoviruses are acknowledged as effective as chemical pesticides in controlling specialized insect pests. An example of a baculovirus that is being optimized for modern technology is the gypsy moth nuclear polyhedrosis virus (LdNPV), used to aerially spray thousands of acres of forest each year.

New research has demonstrated the use of viruses, genetically engineered that assemble active battery materials into a dense, regular structure, to create an ultra-thin, transparent battery electrode that stores approximately three times as much energy as those in lithium-ion batteries. It is the first step toward high-capacity and self-assembling batteries (Marilyn J. Roossinck, 2015). The M13 viruses, made of proteins, most of which coil to form a long, thin cylinder is used to make the positive electrode of a lithium-ion battery which is consequentially tested with a conventional negative electrode. The addition of nucleotide sequences to viral DNA, direct these proteins to form with an additional amino acid that binds to cobalt ions. Thereafter, viruses with these new proteins coat themselves with cobalt ions in a solution, which eventually leads, after reactions with water, to cobalt oxide, an advanced battery material with much higher storage capacity than the carbon-based materials now used in lithium-ion batteries
Another study has described the use of recombinant M13 phage particles as organic templates to polymerize nanowires as building blocks for semiconductors or magnetic materials ((Marilyn J. Roossinck, 2015).

Used to produce vaccines: Recombinant vaccines
Vaccination has been one of the most important interventions designed to prevent diseases to be employed on a worldwide basis, second only to the improvement of sanitation services and the provision of clean drinking water (Reyes-Sandoval and Ertl, 2001)
Robinson HL, 2002 stated that viral vectors are critical in the field of vaccinology. Conventional antibodies have been effective in the aversion and eradication of a few uncontrollable diseases since these methodologies create immunizations, they were exact and reliant upon the enlistment of killing antibodies to develop protection. However, for some developing illnesses, these approaches may not be effective, for the most part, and the need to create a wide range of insusceptible reactions including neutralizing antibodies, white blood cell reactions, and mucosal insusceptibility is vital since they are associated with immune security. Diseases that require a broader resistant reaction, for example, HIV and intestinal sickness, viral vectors may constitute the pivotal role in the development of a successful vaccine.

Normally, vaccines that are gene-based can stimulate powerful humoral and cellular immune responses. Therefore, viral vectors serve as an effective strategy for both the transport of antigen-encoding genes and the facilitation and enhancement of antigen appearance.
Viral vectors have several prospective advantages, compared to traditional vaccine technologies, since they carry unique characteristics. For example, the Avipoxvirus is extremely safe and does not replicate in mammalian cells, these vectors elicit less of a vector-particular immune reaction contrasted with attenuated vaccinia strains and can be utilized for boosting a few times (Robinson HL, 2002). They are in charge of encouraging the generation of elevated amounts of proteins inside transduced cells, among these cells are antigen-introducing cells which constitute an essential subset that can be directed by various viral vectors, making the transgenic protein available to the immune system. Furthermore, the vector can produce a steady impact improving the resistant reaction against the transgenic protein. The viability of controlling viral vector-determined immunizations in blend modalities with different antibodies gives these antibodies a supplementary preferred advantage.
Recombinant viruses are being recognized as important methods in vaccinology both for enhancing existing antibodies and for evolving new ones. This procedure regularly includes taking an established protected and reliable antibody infection, for example, vaccinia or adenovirus, and altering its genome to incorporate qualities coding for immunogenic proteins from different pathogens (Souza et al., 2005). An extensive variety of infections have been widely contemplated for their potential as recombinant antibodies through their own one of a kind attributes, they all can initiate humoral, as well as cell resistant reactions.

Allow for evolution
Viruses are the most abundant and diverse biological entities on the planet. Recent biodiversity surveys in desert, ocean, soil, mammalian gut, and plant ecosystems have uncovered an abundance of viruses in every ecosystem and lifeform examined (Zablocki et al., 2016). These ecological surveys also highlight a common misconception concerning viral biology: In spite of their ubiquitous incidence, most viruses produce no recognizable symptoms associated with diseases (Breitbart and Rohwer, 2005) and that the relations among viruses and their respective hosts are dynamic and variable constituting important forces which shape populations.

In marine virus–bacterial systems, viruses ensure a high level of genetic diversity by continuously infecting different populations at different time intervals preventing the expansion of resistant microbes (Avrani et al., 2012.).

Evidently, viruses have been playing their role in the environment for a long time, since relatives of the human polio pathogen infect plankton organisms. Viruses have accompanied the evolution of cellular living organisms for billions of years – and significantly influenced them. Thus, viruses are now “suspected” of transporting genetic information from one organism to another like a taxi, thereby advancing evolution.

The Human Genome Project revealed that the human genome has abundant viral gene sequences which make themselves evident by special DNA sequences that flank them- between two columns were once retroviruses, belonging to the same group as the AIDS pathogen, for instance. This genetic material is no mere vestige of a past battle, but carries out functions, although viruses characteristically are some of the most rapidly mutating organisms the sequences of endogenous retroviruses seem to be astonishingly well-preserved. Normally, a sequence that has remained unchanged for a long period indicates that the respective gene is needed by the organism ().

Research indicates that about 15 million years ago, a retrovirus was built into the human genome and has now revealed itself to be an aid against cancer, since this so-called endogenous viral DNA strengthens the production of a control factor in the precursor cells of male gametes, thus promoting the “suicide” of defective cells. Plausibly this knowledge can be applied at some point in developing a therapy for testicular cancer. 
Moreover, investigation of the recently gathered human genome uncovered that ?8% of the hereditary material was obtained from retroviral inceptions. These endogenized viral pieces can fill in as a vast supply of cis-regulatory components (e.g., promoters and transcriptional controllers) and as protein-coding locales encompassed by the host (Chuong et al., 2016). These endogenization occasions presented major developmental advancements that give a specific favorable position to the host.
The prevalence and abundance of viruses in certain societies have been used as indicators of origin of distinct viruses and diseases amongst populations. This role is extremely important, as the use of a virus can pinpoint the source of a disease and allow for prevention and therapy treatments to be obtained or optimized.

A beneficial illustration is the Human T-lymphotropic virus type 1 (HTLV-1), found in indigenous populations of the Pacific Islands and America, though type 2 (HTLV-2) is generally dispersed among the indigenous groups of America, suggesting that HTLV-1 being more pervasive than HTLV-1, and in a few clans of Central Africa. HTLV-2 is viewed as ethnic in America and is transmitted to the overall public due to drug abuse. In America, HTLV-1 has in excess of one origin, being brought by outsiders in the Paleolithic time frame through the Bering Strait, and slave exchange amid the frontier time frame, and through Japanese movement from the mid twentieth century, while HTLV-2 was brought by migrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous individuals of Brazil makes the Brazilian Amazon the biggest endemic zone on the planet for this event.
.Research for cancer cells
A type of virus that targets, infects and lyses cancer cells but not normal cells to achieve a strong cytolytic effect are oncolytic viruses. Oncolytic viruses can occur naturally or synthesized in the laboratory by altering other viruses. Certain oncolytic viruses are being studied in the treatment of cancer since they may make it easier to kill tumor cells with chemotherapy and radiation therapy.

Progressed metastatic growths are generally hopeless and the most recent quite a few years of investigation into the science of malignancy has made it unmistakable exactly why this is. Diseases have discovered numerous distinctive approaches to usurp flagging pathways to pick up a development advantage, making it far-fetched that pharmacological assault on a solitary atomic target will fundamentally affect the long haul movement of the danger (Jones et al., 2008) Moreover, tumor cells have turned out to be exceptionally heterogeneous (hereditarily and phenotypically) as they advance under the specific weight of their microenvironment (Melcher et al., 2011).
The inquiry emerges “how to manage the chameleon-like conduct of developing malignancies” that enables them to escape restorative mediation. The present contention is the improvement of a restorative methodology that can coordinate the heterogeneity of a tumor and use the same actuated pathways that drive tumor cell development since our insusceptible frameworks have the ability to quickly react and advance to manage a huge swath of complex attacking microorganisms and unquestionably can possibly perceive the antigenic varieties displayed by dangerous cells ((Subarsky and Slope, 2003).
Infections, then again, have developed to exploit a considerable lot of the same pathways that growth cells enact amid their dangerous movement and inalienably initiate both intrinsic and versatile invulnerable reactions (Kim et al., 2010). Late clinical and preclinical examinations contend that there is a critical transaction amongst viral and invulnerable treatment ways to deal with growth and that keen banding together of these techniques could turn the tide on tumor.Several viruses have been engineered to express di?erent cytokines or chemokines. Cytokines and chemokines are attractive transgenes, encoded by small genes and are generally easy to build in a viral genome. In addition, they often have pleiotropic e?ects, weighing that they can target di?erent immune cells simultaneously.

The use of genetically engineered, tumor-targeting viruses as oncolytic agents has emerged as a promising new area for novel cancer therapies. The first viruses to enter the clinic, ONYX-015 (an oncolytic adenovirus), demonstrated both the safety and anti-tumor potential of this approach. The results of these early trials have allowed investigators to examine the restrictions and limitations of these viruses, and to develop potentially far more effective approaches.

The virus itself can destroy tumor cells by replicating. This cycle can then be repeated, by infection of adjacent cells and their successive destruction by the same mechanism. This feature of viral replication provides continuous amplification of the input dose which continues until stopped by the immune response or a lack of susceptible cells (Subarsky and Hill, 2003). The second mechanism, in which some oncolytic viruses synthesize certain proteins during replication that are directly cytotoxic to cancer cells.

NV1020 is a novel, multi-mutated, replication-restricted HSV currently under investigation for its ability to selectively kill tumors by direct cell lysis. NV1020 efficiently kills human lung cancer lines in vitro and is effective in reducing tumor burden in a rat model of pleural cancer. Moreover, NV1020 is safe when administered intrapleurally in rats. These initial results have encouraged further studies with NV1020 for the treatment of pleural cancers, both metastatic and primary (Ebright et. al, ____).

Figure 2: Diversity of oncolytic viruses and their modes of action.
Given the correct conditions, infections are equipped for focusing on and annihilating growth cells in human tumor patients. Malignancy quality treatment is a quickly developing field which, with no uncertainty, will be a piece of future disease treatments.

Mammalian Health
In warm blooded animals, ERV qualities have kept up a portion of their capacities, including fusogenicity, acknowledgment of speci?c cell receptors, and safe suppressive movement (Esnault et al., 2013). The taming of the endogenized env quality is the forerunner of the syncytin quality in well evolved creatures, a critical quality required in the arrangement of the placenta, a basic organ whose primary capacity is the arrangement of fetal-maternal interface that offers help for the creating developing life by intervening metabolic trades (Esnault et al., 2013).
Retroviral long terminal repeats (LTRs) work as promoters and enhancers that regularly control viral articulation and translation. One of the most punctual depicted illustrations is the declaration of the starch-processing chemical amylase in human spit that outcomes from the addition of an ERV-gave promoter (Meisler and Ting, 1993) despite the fact that the full significance of salivary amylase isn’t clear.The expression of this gene not only spearheaded human evolution but is one of the core genes that provide significant differences between humans and apes by allowing humans to eat novel foods.
The focal limit of retroviruses to coordinate their genomes into the chromatin of target cells makes it conceivable to accomplish changeless transgene articulation with retrovirus-inferred vectors. This element is particularly important with regards to quality treatment for monogenetic clutters, which depends on the stable, ideally deep rooted articulation of a restorative transgene. Notwithstanding this standard approach, ongoing advances have extended the collection of retrovirus-based advances by the improvement of non-incorporating cell change modes that can be connected in situations where a transient jolt is adequate or even required, for instance for the conveyance of lethal hereditary items.
In 2011, scientists distributed long haul survival information for two UK quality treatment preliminaries for SCID. The specialists had extricated the patients’ bone marrow, embedded a working duplicate of the illness causing quality, and mixed the adjusted cells once again into the patients. Up to 9 years after treatment, 14 of the 16 youngsters treated have had their safe frameworks reestablished and have possessed the capacity to live generally typical lives free of any air pockets. Numerous other quality treatment preliminaries are at present in progress—and yielding positive outcomes—for various different sicknesses, including different types of inherited visual deficiency, HIV, hemophilia, neurodegenerative illnesses, and an assortment of diseases. In spite of the fact that no quality treatments have yet gotten FDA endorsement, almost 2,000 clinical preliminaries have been started over the most recent 5 years alone. Notwithstanding, on the grounds that numerous people as of now convey antibodies to adenovirus, the colossal disadvantage of this approach is the danger of immunotoxicity, which can incapacitate the remedial vector or cause reactions in the host. It was an outrageous response to an adenoviral vector that executed the host in the early investigations. Since adenoviruses are effective at entering numerous phone composes and conveying the merchandise, they are focuses of serious research to make them more secure for the treatment of growth, diabetes, HIV, and hereditary illnesses.The lentivirus, for example, HIV, is a type of RNA retrovirus that delivers its contents to the cytoplasm, where a reverse transcriptase converts it into DNA. The DNA then enters the nucleus, where it inserts into the genome. This integration ensures that the therapeutic DNA will be passed onto daughter cells, making them efficient at delivering and establishing stable high levels of transgene expression in both dividing and non-dividing cells. As an alternative to injecting the viral vector directly into a patient, researchers can extract a patient’s cells, such as those of the bone marrow, infect them with the lentivirus vector in culture, then infuse the modified cells back into the patient’s body. The risk that integration will trigger a disease-causing mutation is reduced because, unlike some retroviruses, lentiviruses don’t tend to integrate into oncogenes or growth-related genes. Lentiviruses have a sizeable carrying capacity, 9 kilobases of genetic material. Researchers only have to delete a few genes to get lentivirus to carry twice as much as AAVs. Many clinical trials to deliver treatments for a variety of eye diseases (wet age-related macular degeneration, Stargardt disease, Usher syndrome, and corneal graft rejection) are underway.

The flavivirus GB virus C (GBV-C, also designated hepatitis G virus) was identified in a search for hepatitis viruses, though no disease is currently known to be associated with it. Coinfection with GBV-C is related with a decreased death rate in HIV-tainted patients. GBV-C isn’t known to cause any sickness, however it is conceivable that its essence prompts a hindrance of HIV replication. Nonetheless, GBV-C disease could likewise be a marker for the nearness of different variables that prompt an ideal HIV reaction (N Engl J Med 2001; 345: 715-24.).
Contamination with GB infection C is asymptomatic in people and could be viewed as a commensal infection, however under a few conditions, it turns into a mutualist. Patients who are HIV positive show slower movement of sickness when they are contaminated with GB infection C. A few consequences for HIV, including downregulation of cell receptors for passage, diminished replication, impacts on interferon blend, and associations with interleukin pathways, have been seen in clinical investigations and in vitro (Bhattarai and Stapleton, 2012). Most bacterial pathogens of people are empowered by their phages. Phages are engaged with the even quality exchange of basic components, either by coordinate techniques, for example, joining into have genomes (lysogeny) and transduction or by backhanded strategies, for example, the change of DNA from lysed cell flotsam and jetsam (Gilbert et al., 2016). Coordination of calm infections could furnish the bacterial host with numerous preferences over its non-tainted partners, for example, better protection from natural stressors and new cell works and additionally a wellspring of assurance from different infections through superinfection avoidance, regulation of host digestion through articulation of assistant metabolic qualities, qualities that are not engaged with infection replication and capacity but rather that adjust have metabolic procedures that support infection replication (Brum et al., 2016).

Bacteriophages and their influence on human health
Bacteriophages (phages), the most abundant entities on earth, are viruses which infect bacteria and often kill them by using the cell as a factory for the production of new viral copies and dissolving the cellular envelope to release the progeny viruses. A single viral genome delivered by a single phage is sufficient to take control of the entire cell and divert the resources to assemble viruses.

Most bacterial pathogens of people are empowered by their phages. Phages are engaged with the even quality exchange of basic components, either by coordinate techniques, for example, joining into have genomes (lysogeny) and transduction or by backhanded strategies, for example, the change of DNA from lysed cell flotsam and jetsam (Gilbert et al., 2016). Coordination of calm infections could furnish the bacterial host with numerous preferences over its non-tainted partners, for example, better protection from natural stressors and new cell works and additionally a wellspring of assurance from different infections through superinfection avoidance, regulation of host digestion through articulation of assistant metabolic qualities, qualities that are not engaged with infection replication and capacity but rather that adjust have metabolic procedures that support infection replication (Brum et al., 2016).

For centuries, viruses, the most abundant and mutagenic, have been considered pathogenic and associated with diseases and plagues. However, viruses are now being recognized for their active roles in society and their ability to shape the human evolution, both intrinsically and extrinsically. Their roles in immunity response, mammalian health and population control along with their ability to be manipulated for modern technology put them in the forefront of medical innovations. The use of viruses has evolved exponentially over the past few decades that we can now map out the source and location of a virus and develop specific vaccines for that population.
The prospects and applications of viruses can turn the tide on both HIV/ AIDS and cancer.

In the end, it poses the question, without viruses where would we be?
Alan Melcher, Kelley Parato, Cliona M Rooney and John C Bell, 2011.Thunder and Lightning: Immunotherapy and Oncolytic Viruses Collide. The American Society of Gene ; Cell Therapy.

A.P.D. Souza, L. Haut, A. Reyes-Sandoval and A.R. Pinto, 2005. Recombinant viruses as vaccines against viral diseases. Brazilian Journal of Medical and Biological Research 38: 509-522
Avrani S, Schwartz DA, Lindell D. 2012. Virus-host swinging party in the oceans. Mob. Genet. Elem. 2:88–95
Bhattarai N, Stapleton JT. 2012. GB virus C: the good boy virus? Trends Microbiol. 20:124–30
Breitbart M, Rohwer F. 2005. Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 13:278–84
Brown SP, LeChat L, DePaepe M, Taddei F, 2006. Ecology of microbial invasions: Ampli?cation allows virus carriers to invade more rapidly when rare. Curr. Biol. 16:2048–52
Brum JR, Hurwitz BL, Scho?eld O, Ducklow HW, Sullivan MB. 2016. Seasonal time bombs: Dominant temperate viruses affect Southern Ocean microbial dynamics. ISME J. 10:437–49
Cheever, MA, Allison, JP, Ferris, AS, Finn, OJ, Hastings, BM, Hecht, TT et al. (2009). The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res 15: 5323–5337.

Chuong EB, Elde NC, Feschotte C, 2016. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351:1083–87
Esnault C, Cornelis G, Heidmann O, Heidmann T. 2013. Differential evolutionary fate of an ancestral primateendogenousretrovirusenvelopegene,theEnvVsyncytin,capturedforafunctioninplacentation. PLOS Genet. 9:e1003400
Jones, S, Zhang, X, Parsons, DW, Lin, JC, Leary, RJ, Angenendt, P et al. (2008). Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321: 1801–1806.

Kim, M, Williamson, CT, Prudhomme, J, Bebb, DG, Riabowol, K, Lee, PW et al. (2010). The viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status. Oncogene 29: 3990–3996.

Mai-Prochnow A, Hui JGK, Kjelleberg S, Rakonjac J, McDougald D, Rice SA. 2015. Big things in small packages: the genetics of filamentous phage and effects on fitness of their hsots. FEMS Microb. Rev. e-pub ahead of press.
Marilyn J. Roossinck, 2015. Move Over, Bacteria! Viruses Make Their Mark as Mutualistic Microbial Symbionts. Journal of Virology Jun 2015, 89 (13) 6532-6535; DOI: 10.1128/JVI.02974-14
Marilyn J. Roossinck and Edelio R. Baz´an, 2017. Symbiosis: Viruses as Intimate Partners. Center for Infectious Disease Dynamics, Department of Plant Pathology and Environmental Microbiology, Pennsylvania State University, University Park, Pennsylvania 16802.

Gilbert C, Peccoud J, Chateigner A, Moumen B, Cordauz R, Herniou EA. 2016. Continuous in?ux of genetic material from host to virus populations. PLOS Genet. 12:e1005838
Márquez LM, Roossinck MJ. 2012. Do persistent RNA viruses fit the trade-off hypothesis of virulence evolution? Current Opinion in Virology 2:556-560.

Meisler MH, Ting C.1993. The remarkable evolutionary history of the human amylase genes. Crit. Rev. Oral Biol. Med. 4:503–9
Michael I. Ebright, Jonathan S. Zager, Sandeep Malhotra, Keith A. Delman, Tracey L. Weigel, MD Valerie W. Rusch and Yuman Fong: Replication-competent herpes virus NV1020 as direct treatment of pleural cancer in a rat model. J Thoracic Cardiovasc Surg 124(1)
Nakatsukasa-Akune M, Yamashita K, Shimoda Y, Uchiumi T, Abe M, Aoki 232 T, Kamizawa A, Ayabe S-i, Higashi S, Suzuki A. 2005. Suppression of root nodule formation by artificial expression of the TrEnodDR1 (coat protein of White clover cryptic virus 2) gene in Lotus japonicus. Mol. Plant-Microbe Inteact. 18:1069-1080
Reyes-Sandoval A, Ertl HC, 2001. DNA vaccines. Current Molecular Medicine, 1: 217-243.

Robinson HL, 2002. New hope for an AIDS vaccine. Nature Reviews. Immunology, 2: 239-250.

Roossinck MJ. 2012. Persistent Plant Viruses: Molecular Hitchhikers or Epigenetic Elements?, p. 177-186. In Witzany G (ed.), Viruses: Essential Agents of Life. Springer, Dordrecht.
Schmitt MJ, Breinig F. 2006. Yeast viral killer toxins: lethality and self-protection. Nat. Rev. Microbiol. 4:212–21
Shapiro LR, Salvaudon L, Mauck KE, Pulido H, DeMoraes CM, Stephenson AG, Mescher MC. 2013. Disease interactions in a shared host plant: effects of pre-existing viral infection on Cucurbit plant defense responses and resistance to bacterial wilt disease. PLoS One 8:e77393
Subarsky, P, and Hill, RP (2003). The hypoxic tumor microenvironment and metastatic progression. Clin Exp Metastasis 20: 237–250.

Tillmann HL, Manns MP. GB virus-C infection in patients infected with the human immunodeficiency virus: evidence for a beneficial influence of GBV-C on HIV infection and discussion of possible mechanisms of their interactions. Antiviral Res (in press).

Virgin HW. 2014. The virome in mammalian physiology and disease. Cell 247 157:142-150.

Wächtler M, Hofmann A, Müller G, et al. Prevalence of GB virus C/ hepatitis G virus RNA and anti-E2 glycoprotein antibodies in homosexual men with HIV coinfection. Infection 2000;28:297-300.
Xiang J, Wünschmann S, Diekema DJ, et al. Effect of coinfection with GB virus C on survival among patients with HIV infection. N Engl J Med 2001;345:707-14.

Xu P, Chen F, Mannas JP, Feldman T, Sumner LW, Roossinck MJ, 2008. Virus infection improves drought tolerance. New Phytol. 180:911–21
Zablocki O, Ardriaenssens EM, Cowan D. 2016. Diversity and ecology of viruses in hyperarid desert soils. Appl. Environ. Microbiol. 82:770–77