Archives of Virology (2018) 163:821–830 https://doi.org/10.1007/s00705-017-3686-5
REVIEW
Enemies with benefits: mutualistic interactions of viruses with lower eukaryotes Shounak S. Jagdale1 · Rakesh S. Joshi1 Received: 8 July 2017 / Accepted: 6 November 2017 / Published online: 6 January 2018 © Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract Viruses represent some of the deadliest pathogens known to science. Recently they have been reported to have mutualistic interactions with their hosts, providing them direct or indirect benefits. The mutualism and symbiogenesis of such viruses with lower eukaryotic partners such as fungi, yeast, and insects have been reported but the full mechanism of interaction often remains an enigma. In many instances, these viral interactions provide resistance against several biotic and abiotic stresses, which could be the prime reason for the ecological success and positive selection of the hosts. These viruses modulate host metabolism and behavior, so both can obtain maximum benefits from the environment. They bring about micro- and macrolevel changes in the hosts, benefiting their adaptation, reproduction, development, and survival. These virus-host interactions can be bilateral or tripartite with a variety of interacting partners. Exploration of these interactions can shed light on one of the well-coordinated biological phenomena of co-evolution and can be highly utilized for various applications in agriculture, fermentation and the pharmaceutical industries.
Introduction Viruses are intracellular parasites, with genomes capable of directing their own replication. Classically they are classified as non-cellular entities with an extrachromosomal phase, without any essential function to their host [1]. Viral pathogenicity is well studied through the various aspects of immunology, vaccine development, and genetic engineering. Recently, researchers have identified mutualistic viruses of different organisms, but their replication and mechanism of interaction with the host still remains ambiguous. Discovery of such interactions has modified the definition of viruses, to account for mutualistic viruses, as ‘intracellular parasites, with nucleic acids that are capable of directing their own replication, and are not cells’ [1]. Mutualism is part of a very broad concept called symbiosis, which is an umbrella term that includes parasitism, commensalism and mutualism – wherein both partners benefit from each other. The integration of two different organisms Handling Editor: Robert H.A. Coutts. * Rakesh S. Joshi
[email protected];
[email protected] 1
Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune, Maharashtra 411007, India
that results in the formation of a new species is a theory of evolution called symbiogenesis [2]. A fusion of the virus with its host has been observed in interactions prevailing since ancient times, termed as viral symbiogenesis. Various mutualistic and symbiogenetic viruses of lower eukaryotes and their effects on host survival and adaptation are discussed here (Table 1).
Endophytic fungi and viruses Mycoviruses are dsRNA viruses that infect fungi. These viruses are host dependent and their persistent infection leads to long-term transmission. In many cases, mycoviruses infect the host multiple times, thereby aiding the host’s genetic variability, without causing any detrimental effects [3]. Recently, symbiotic effects of mycoviruses on various traits of endophytic fungi have been documented, expounding a three-way symbiotic relationship amongst plants, fungi, and viruses [4]. In the case of a thermotolerant panic grass, Dichanthelium lanuginosum, three-way symbiosis has been described. The prime reason behind the growth of these plants in geothermal soils (65 °C) was thought to be due to its association with a fungus named Curvularia protuberata [5]. However, the third partner of this system was found to be a virus, the Curvularia
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thermal tolerance virus (CThTV) which is responsible for conferring thermal tolerance to the plant [Figure 1]. The spherical virus, with a diameter of 27 nm, contains 2 RNA segments of 2.2 and 1.8 kb. Each of the 2 strands contain 2 ORFs. ORFs of RNA1, namely ORF1a and b, overlap each other and show sequence similarity to RNA-dependent RNA polymerases (RdRp). RNA2 ORFs show no sequence similarity with sequences currently available. The vertical transmission of the virus takes place through conidiospores [6]. Virus infected C. protuberata show a two-fold increase in the expression of trehalose phosphate synthase (TPS) leading to increased levels of an osmoprotectant trehalose - that maintains protein and membrane integrity under environmental stress conditions [7, 8]. Furthermore, metabolic overexpression of mannitol, a potential osmoprotectant, is also observed in the hyphae [9]. Similarly, upregulation of the homologs of betaine aldehyde dehydrogenase (BadH) and taurine catabolism dioxygenase Fig. 1 Three-way symbiotic relationship amongst plant, endophytic fungus and a virus. D. lanuginosum shows enhanced thermal tolerance [65 °C]. This thermal tolerance is acquired due to the presence of a dsRNA virus CThTV residing within an endophytic fungus C. proturberta
(TauD) leads to enhanced synthesis of osmolytes and osmoprotectants, namely glycine betaine and taurine [7, 10, 11]. In addition, an elevated level of melanin due to overexpression of scytalone dehydratase (SCD), provides protection from extreme temperature and radiation [7, 12]. Plants colonized by CThTV-infected C. protuberata show constitutive overexpression of osmolytes when compared to normal plants [6]. However, the exact mechanism of this virus mediated thermal tolerance in plants is still unclear. It was reported that C. protuberata could colonize various plants such as Oryza sp., Triticum sp., Solanum lycopersicum and Cucurbita pepo [13]. In S. lycopersicum, thermal tolerance is observed when associated with CThTV infected C. proturberata [6, 14]. Thus, this mechanism of virus infection-mediated thermal protection can be applied to other plants for the development of abiotic stress tolerance.
Infection of CThTV
C. proturberta
Increased Thermo tolereance D. lanuginosum
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Mutualistic viruses of yeast Over the course of evolution, various organisms have developed tactics to overcome competition. For example, yeasts such as Saccharomyces cerevisiae, Ustilago maydis and Zygosaccharomyces bailii utilize viral assisted toxin production to kill competing yeast colonies, and are thus called ‘killer yeast’ [15]. The totivirus Saccharomyces cerevisiae virus L-A (ScV-L-A) present in the yeast helps in the stable maintenance and replication of satellite viruses namely S. cerevisiae virus M1 (ScV-M1), ScV-M2 or ScV-M28. Infection of ScV-M1, ScV-M2 or ScV-M28 in S. cerevisiae results in the production of toxins, namely K1, K2 and K28 [16–19]. ScV-L-A and ScV-M viruses show cytoplasmically-inherited, symptomless infection of killer yeast. ScV-L-A has 2 ORFs which encode gag and pol. The virus capsid protein consists of 120 copies of gag and 2 copies of a gag-pol fusion protein. The satellite viruses have only 1
ORF which encode the killer pre-protoxin. Satellite viruses parasitize the helper virus for the production of their capsid proteins [20]. Subsequently, the toxins produced, act on sensitive yeast colonies in a two-step process: The first step is energy independent wherein, the toxin binds to the cell wall receptor of sensitive yeast. K1 and K2 bind to β-1,6D-glucan, whereas K28 binds to α-1,3-mannoprotein [21, 22]. The second step is energy dependent, where the toxin translocates to the cytoplasmic membrane and interacts with a secondary receptor [Figure 2]. For K1, this receptor is a GPI-anchored plasma membrane protein Kre1P and for K28, it is cellular HDEL receptor Erd2P [23, 24]. Interaction of K1 with Kre1P results in the formation of an ion channel, disrupting the cytoplasmic membrane [25–27]. K28, after binding to α-1,3-mannoprotein, is taken up by endocytosis and is targeted to early endosomal compartments. From there, it enters the cell cytosol through the secretory pathway and blocks cellular DNA synthesis, arresting the cells in early S phase [28].
Sensitive yeast
ScV-L-A
ScV-M
ScV-M
K1, K2 or K28 toxin
Erd2P
Kre1P
Ion-channel formation in the cytoplasm by K1 toxin
β-1-6 D-Glucan and α-1-3- mannoprotein K28 endocytosis
Block in DNA synthesis by K28 toxin
Killer yeast
Fig. 2 Killer yeast mechanism of action. Killer yeast harbour the satellite M viruses which parasitize the helper L-A virus for coat proteins. M viruses then produce the toxins K1, K2 or K28 which act on the sensitive yeast colonies in a 2-step process. Toxins first bind to cell wall receptors β-1,6-D glucan and α-1,3-manonprotein fol-
lowed by binding to plasma membrane receptors Kre1P and Erd2P. Once inside the sensitive yeast cell, K1 toxin results in ion channel formation in the cytoplasmic membrane and K28 translocates to the nucleus blocking DNA synthesis
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It is critical for the killer yeast to be immune to these toxins. Killer yeast immunity against these toxins involves the K1 toxin precursor, which acts as a competitive inhibitor of the active toxin by saturating the plasma membrane receptor. In the case of K28 toxin, the active toxin taken up by killer cells binds to the pre-protoxin present in the cytosol. This protein complex is then ubiquitinated and degraded by the proteasome machinery [29]. Both helper and satellite viruses are dependent on the expression of several yeast chromosomal genes. Amongst these, MAK3 encodes an N-acetyltransferase which acetylates the capsid proteins allowing their self-assembly [30]. MAK10 which encodes N-acetyltransferase, and PET18 that encodes thiamin metabolism protein, are necessary for the stabilization and replication of viral particles [31]. Furthermore, SEC genes are required for extracellular protein secretion [32]. KEX encoded proteases, Kex1p and Kex2p are necessary for the pre-protoxin processing [33]. This clearly suggests a mutualistic relationship between these viruses and yeast. Other than Saccharomyces, yeasts like Hanseniaspora uvarum and U. maydis also show the presence of killer viruses. The toxins generated by these viruses show a broad spectrum antimycotic effect [15]. There are many applications of these viral toxins in the fermentation and pharmaceutical industries. During wine fermentation, killer yeasts are used to eradicate contaminating yeasts [34]. As the killer toxins selectively target the cell wall components of yeasts and fungi, they also have potential uses in the topical treatment of fungal diseases. Recently studied toxins, wicaltin and zygocin produced by Williopsis californica and Z. bailii respectively, showed effective antifungal activity [35, 36]. Other than fungi, these kinds of mutualistic interactions are also observed in insects, as will be discussed later.
Symbiogenic viruses of insects Viruses show diverse and dynamic interactions with various insects. Symbiogenesis between polydnaviruses (PDVs) and endoparasitoid wasps is well studied. PDVs are dsDNA viruses which have prevailed across generations as proviruses meaning they are integrated in the host genome. In several species of braconid and ichneumonid wasps these are called bracoviruses and ichnoviruses, respectively. These wasps are primary endoparasites of coleopterans, dipterans, and lepidopterans. They oviposit in insect larvae, triggering the innate immune response of the larvae resulting in encapsulation of the eggs by larval hemocytes. PDVs suppress the insect immune response and help the wasp eggs’ survival [37]. PDVs replicate in the calyx of the oviduct of the female wasp and get transmitted to the wasp host insect during oviposition [38]. Upon infection, viral gene expression results in morphological alteration and apoptosis of host
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hemocytes, creating favorable conditions for the survival of wasp eggs and larval development [39, 40]. The Cotesia congregrata bracovirus (CcBV) genome contains 156 genes; 27 genes encoding protein tyrosine phosphatases and 6 for proteins with ankyrin repeat motifs from the IκB family, which inhibit the immune responses. Four genes code for cysteinerich cysteine knot motif proteins, similar to the teratocyte secreted protein 14 (TSP 14) which inhibits the translation of storage proteins in the hosts, resulting in developmental defects. Furthermore, 3 genes code for cystantin superfamily cysteine protease inhibitors with immunosuppressive roles [41]. PDVs and parasitoid wasps have co-evolved over 73 million years [42]. Their phenomenal symbiogenic interaction blurs the boundaries that make them two separate entities [43]. The strong antagonistic effect of PDVs on wasps’ insect hosts, results in a favorable condition for wasp’s eggs survival and larval development, which could be the prime reason for wasp-PDV symbiogenesis. In contrast, recurrent infection by PDVs has triggered horizontal gene transfer (HGT) between the virus and lepidopteran host, which is beneficial to the wasp’s host. HGT of two genes, BV2-5 and BLL-2, has been observed in Spodoptera sp., providing it resistance against baculoviruses such as nuclear polyhedrosis virus (NPV), which are used as biopesticides. BV2-5 interferes with baculovirus motility and replication while BLL-2, a bracoviral homolog of C-lectin, blocks baculoviral infection in insects [44].
Mutualistic viruses of insects Mutualistic viruses of parasitoid wasps include ascoviruses and reoviruses. In Diadromus pulchellus, the Diadromus pulchellus ascovirus 4 (DpAV4) genome is maintained in the wasp cell nuclei as an episome, which does not integrate into the host genome. This virus is ellipsoid in shape, about 220 nm long and 150 nm wide with a genome size of 116 kb. As the wasp deposits eggs in the host, Acrolepiopsis assectella, virions are also injected. Post infection, viral replication begins in synchrony with the wasp egg development. DpAV4 affects host metabolism and inhibits melanization, protecting the wasp eggs from encapsulation [45]. Additionally, D. pulchellus reovirus 2 (DpRV2) also has similar effects on A. assectella [46]. In the case of the spotted lady beetle Coleomegilla maculata, Dinocampus coccinellae is the primary endoparasitic wasp. In the wasp, a ssRNA virus Dinocampus coccinellae paralysis virus (DcPV), is present within large vesicles in the cellular lining of the female wasp oviduct. The virus genome is about 10 kb in size and has one large ORF which encodes a precursor polyprotein. The N-terminal part of the polyprotein encodes viral structural proteins, whereas the C-terminus encodes an RdRp. Female
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wasp oviposit in the lady beetle and the larva develops inside the beetle’s body. After 20 days, the larva egresses and spins a cocoon between the beetle’s legs. At this time, the beetle gets paralyzed and becomes the unwitting protector of the cocoon [47]. This phenomenon is termed as ‘Bodyguard Behavior’, which is due to the wasp symbiont DcPV [Figure 3]. Inside the beetle, the DcPV population is very low during the early wasp-egg developmental period. The DcPV population only starts increasing post wasp-egg hatching. Just before the larvae egress, DcPV infects the glial cells of the beetle. Immediately after egression, vacuolization of glial cells, axonal swelling, and phagosomal activity in the CNS results in neuronal degeneration consequently altering the behavior of the host beetle. Apart from this, suppression of the beetle’s viral immune response is also observed during infection. After pupation, the viral load is cleared from the beetle’s body and neuronal restoration is initiated by a still unknown mechanism [48]. Apart from wasps, mutualistic viruses are found in many other insects. A polyphagous lepidopteran Helicoverpa
armigera is one of the most cosmopolitan crop pests. Chemical pesticides, genetically modified crops, and the use of viruses like baculoviruses as biopesticides are common practices for H. armigera control. Recently, H. armigera was found to show an increased resistance against major biopesticides due to the presence of H. armigera densovirus-2 (HaDV-2), previously known as H. armigera densovirus-1 (HaDNV1). HaDV-2 is a dsDNA virus classified within the family Parvoviridae, transmitted vertically through eggs. The genome of the virus is about 5 kb in size and contains 3 ORFs. ORF1 and 2 encode for non-structural (NS) proteins similar to helicase and NS2, respectively. ORF3 on the other hand, encodes a structural protein VP. Insects infected with the virus show an increase in lifespan, weight and fecundity as well as enhanced resistance to cry1Ac and H. armigera nucleopolyhedrovirus infection [Figure 4]. This suggests that HaDV-2 is a mutualistic virus, but its mechanism of interaction is still unknown [49]. Some plant viruses also show similar effects on their insect vectors. Feeding of thrip, Frankliniella occidentalis, on plants leads to the
(Day 0) Oviposition No detectable viral titer in eggs Latent viruses in wasp oviduct
(Day 5) (Day 35)
Adult wasp (Day 25)
Healthy beetle (Day 0)
Neuronal restoration and recovery (Day 35)
(Day 13)
Immunesuppression
(Day 21)
Viral replication in larvae
Larval development
Viral transmission to the beetle cells
Neuronal degeneration (Day 20)
Viral clearance by immune system
Pupation
Fig. 3 Bodyguard behavior in spotted lady beetle. D. coccinellae oviposits in the healthy beetle. The viral titer of DcPV is undetectable in eggs but it increases with the development of the larvae. Just before egression, the virus infects the glial cells causing neuronal degradation which results
Viral infection of the glial cells
in tremors and paralysis in the beetle. The larva then uses the paralyzed beetle as its bodyguard and produces a cocoon below the beetle. The adult wasp leaves the cocoon after development. The beetle’s immune system then clears the viral load and progressive neuronal restoration takes place
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Increased resistance against NPV and Cry1AC Cry1AC
Infection to insect with HaDV-2
NPV
H. armigera
Fig. 4 Mutualistic relationship between H. armigera and HaDV-2. H. armigera larvae are susceptible to HaNPV and cry1Ac toxin. When HaDV-2 is present in the insect, the larvae become resistant to the baculovirus and cry1Ac. The insect also shows increased fitness in the presence of HaDV-2
transmission of tomato spotted wilt virus. Larvae feeding on such virus-infected plants show rapid development, as compared to those feeding on non-infected plants [50]. Similarly, aphids Micromyzus kalimpongensis transmit cardamom bushy dwarf virus, which causes foorkey disease in large cardamom. This virus belongs to the genus Babuvirus of the virus family Nanoviridae. M. kalimpongensis carrying the virus show a significant increase in the fecundity, longevity and growth rate during nymphal instar [51]. Similar to a three-way interaction in fungus-plant-virus, some insects also exhibit a three-way relationship between the host insect, primary endosymbiotic bacteria, and a bacteriophage. An example of this relationship is the defensive symbiosis in aphids Acyrthosiphon pisum, the primary symbiont bacteria Hamiltonella defensa, and a secondary symbiont phage A. pisum secondary endosymbiont (APSE) [52]. One of the most predominant enemies of A. pisum is a wasp Aphidius ervi, which lays eggs in the aphid. Along with oviposition, it injects the aphid with venom which degrades the aphid’s reproductive system [53]. The larvae subsequently feed and develop inside the aphid. When the larvae are fully developed, they feed on the remnants of the aphid and pupate within the hardened cuticle, called a mummy. It has been observed that A. pisum infected with
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H. defensa are less susceptible to A. ervi [54]. Other than A. pisum, this anti-parasitoid role of H. defensa has also been observed in other aphid species due to APSE infection [55, 56]. APSEs are dsDNA viruses with a capsid morphology similar to that of viruses classified within the Podoviridae [57]. APSE contains proteinaceous toxins required by A. pisum for defense against the wasp’s offspring. There are 7 APSE variants based on the eukaryotic toxins and bacterial lysis genes that they encode. On the basis of these toxins, they are distinguishable into 3 groups: cytolethal distending toxin subunit B (cdtB) homolog (APSE 2, 6, and 7), Shiga-like toxin (stx) (APSE 1, 4, and 5), and toxin containing YD-repeat (ydp) (APSE 3) [58]. CdtB has DNase activity which disrupts actively dividing cells, while Shigalike toxins have an N-glycosidase activity that prevents protein synthesis in eukaryotes, by rRNA cleavage [59, 60]. The exact functioning of ydp toxins is still enigmatic. In pea aphids, loss of APSEs results in numerous deleterious effects on aphid fitness by slowing development, causing weight loss, delaying the onset of reproduction, and reducing fecundity. This loss also results in increased titers of H. defensa leading to lethal effect on aphid growth and reproduction, thereby hampering the aphids’ lifecycle [61]. Therefore, APSEs keep a check on the population of primary endosymbionts. Recently, it has been observed that APSEs are also associated with another bacterial symbiont known as Arsenophonus which plays an important role in parasite control [62]. The molecular mechanism of APSEs interactions in Arsenophonus is still under investigation. Aside from these, many more three-way interactions are likely to exist in nature. However, the high degree of complexity of these interactions makes them onerous to detect and study (Table 1). Another example of insect-virus mutualism is the relationship between the parasitic mite Varroa destructor and the deformed wing virus (DMV). V. destructor is an ectoparasite of honey bees, which attaches to the bee’s body and feeds on its hemolymph [63]. The mites transmit the viral pathogen DMV to the honey bees. Upon infection, this virus suppresses the humoral and cellular immune response, which results in phenotypic abnormalities such as damaged appendages, stubby wings, and paralysis of the legs [64–66]. It is hypothesized that the presence of the virus results in increased fitness and in turn, fertility in mites [67]. In a few cases, viruses have shown a more complex interaction between antagonism and mutualism with lower eukaryotic organisms. For example, in Drosophila melanogaster, Drosophila C virus (DCV) shows an antagonistic effect in young flies, but mutualistic effects in adults. DCV infection through ingestion boosts the reproductive capacity and decreases the development time of Drosophila [68]. A detailed analysis of these interactions will help to understand the host-virus co-evolution.
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Mutualism between viruses and lower eukaryotes Table 1 Mutualistic viruses of eukaryotes Organism
Virus
Virus family
Virus genus Genome Virus function
References
Unassigned [Mycovirus]
Unassigned dsRNA
Thermal tolerance of the fungus and the associated plants
[6, 14]
Totiviridae Unassigned
Totivirus dsRNA Unassigned dsRNA
[15]
ScV-M2
Unassigned
Unassigned dsRNA
ScV-M28
Unassigned
Unassigned dsRNA
UmV-P1
Unassigned
Unassigned dsRNA
UmV-P4
Unassigned
Unassigned dsRNA
UmV-P6
Unassigned
Unassigned dsRNA
HuV-L HuV-M ZbV-L ZbV-M
Unassigned Unassigned Unassigned Unassigned
Unassigned Unassigned Unassigned Unassigned
W. californica
WcV-M
Unassigned
Unassigned dsRNA
Viruses of insects Braconid wasps
Helper virus A satellite virus. Encodes toxin protein K1 which causes disruption of the cytoplasmic membrane A satellite virus. Encodes toxin protein K2 which causes disruption of the cytoplasmic membrane A satellite virus. Encodes toxin protein K28. Blocks DNA synthesis and causes cell cycle arrest in S-phase Encodes toxin protein KP1 which causes disruption of the cytoplasmic membrane Encodes toxin protein KP4 which blocks calcium uptake of the cell Encodes toxin protein KP6 which causes disruption of the cytoplasmic membrane Helper virus Satellite killer virus Helper virus A satellite virus. Encodes toxin protein zygocin which causes disruption of the cytoplasmic membrane A satellite virus. Encodes toxin protein wicaltin which causes disruption of cell wall disruption and inhibition of cell wall regeneration
Bracovirus Polydnaviridae Bracovirus
Suppression of the host immune response resulting in generation of favorable conditions for the wasp larval development Ichneumonid wasps Ichnovirus Polydnaviridae Ichnovirus dsDNA Suppression of the host immune response resulting in generation of favorable conditions for the wasp larval development D. pulchellus DpAV4 Ascoviridae Ascovirus dsDNA Inhibition of melanisation in host insect D. pulchellus DpRV2 Reoviridae Unassigned dsRNA Inhibition of melanisation in host insect D. coccinellae DcPV Iflaviridae Iflavirus +ssRNA Neuronal degeneration in beetle causing bodyguard behavior H. armigera HaDV-2 Parvoviridae Unassigned dsDNA Increased fitness of the host. Resistance against biopesticides cry1Ac toxin and HaNPV F. occidentalis TSWV Tospoviridae Orthoto-ssRNA Rapid insect larval development spovirus M. kalimpongensis CBDV Nanoviridae Babuvirus ssDNA Increased fecundity, longevity and growth rate in nymphal development APSE Podoviridae Unassigned dsDNA Production of toxins against the endoparasitic wasp A. pisum A. ervi. Increased aphid fitness. Keeps the primary H. defensa endosymbiont population in check Arsenophonus V. destructor DWV Iflaviridae Iflavirus +ssRNA Suppression of humoral and cellular response in honey bees causing phenotypical abnormalities. Increased fitness of the mite D. melanogaster DCV Dicistroviridae Cripavirus +ssRNA Increased reproductive capacity and decreased development time in adults
[72]
Viruses of endophytic fungi CThTV D. lanuginosum S. lycopersicum C. proturberta Viruses of killer yeasts S. cerevisiae ScV-L-A ScV-M1
U. maydis
H. uvarum Z. bailli
dsRNA dsRNA dsRNA dsRNA
dsDNA
[69] [70] [29] [35] [37]
[71]
[45] [46] [47, 48] [49] [50] [51] [52] [67] [68]
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Future prospects and conclusion The current knowledge of virus-host mutualism is limited, due to the complexity of these interactions. In many cases, due to a high degree of co-evolution, it is difficult to distinguish between the virus and the host. Sequencing techniques used to study the organization of the PDVs’ genome can be extrapolated to different organisms in order to reveal the presence of mutualistic viruses and elaborate their genomic organization [73]. Once identified, a detailed understanding of viral mutualism at the genetic, transcriptional and translational level is required to delineate the role of viruses in the hosts’ life-cycle. It is clear that many insects are dependent on endosymbiotic bacteria such as Hamiltonella, Wolbachia, and Arsenophonus. However, the recently observed viral mutualism has added another layer of complexity to the understanding of the ecological dynamics of mutualism. A general mathematical model of viral mutualism based on the Lotka-Volterra framework has been described for few virus-host interactions [74]. Similar mathematical models for other mutualistic viruses need to be developed and studied in detail to understand the impact of their relationship on the host population and ecological succession. These interactions could be explored for various biotechnological applications. Several generalist endophytic fungal species need to be investigated for the presence of endophytic viruses like CThTV, which can confer resistance to abiotic stress to host fungus and eventually to the plant colonized by this fungus. Killer viruses containing yeasts are widely used in the fermentation industry to eliminate contaminating yeast colonies however, these viruses could serve as more specific and effective options for the current antifungal compounds for animal and plant fungal infections. The genomic contents of PDVs make them a natural biological weapon harbored in wasps. PDVs express Cys-rich proteins that act as immunosuppressants in host insects. These proteins, similar to TSP14, can be used for the development of transgenic plants which effectively reduce the number of lepidopteran pests like Heliothis virescens and Manduca sexta [75]. Furthermore, cystantins are also used for the development of transgenic plants that could have resistance to nematodes [76]. Other viral proteins can be utilized for the development of novel insecticides. The toxins encoded by APSEs could also be made as novel insecticides. It is clearly evident that viruses are not just pathogenic but also beneficial to their hosts. They are associated with various functions that are essential for the development and survival of their hosts. Detailed analysis of these mutualistic interactions is still lacking and has great scope for future research. With advancements in the fields of
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various omics, more and more viral mutualistic interactions are coming to light. Along with the genomic studies, the effect of these viruses on the organisms’ proteome and metabolome has to be studied to understand these interactions to their fullest extent. Acknowledgements Authors acknowledge Dr. Tuli Dey, Dr. Rohan Khadilkar and Dr. Sneha Bansode for their critical comments. Authors also acknowledge Ms. Yoshita Bhide and Ms. Shriya Lele for their editorial assistance. Author contributions The concept was developed and articulated by SSJ and RSJ. Manuscript was written and edited by SSJ and RSJ. Funding Financial support is provided by the research grant from Department of Science and Technology, Government of India under ECR/2015/000502 Grant and Savitribai Phule Pune University, Pune 411007, Maharashtra India.
Compliance with ethical standards Conflict of interest Authors declare no conflict of interest.
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