| 1. |
- Inturi, Raviteja, 1985-, et al.
(författare)
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Adenovirus Precursor pVII Protein Stability Is Regulated By Its Propeptide Sequence
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80617-
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Tidskriftsartikel (refereegranskat)abstract
- Adenovirus encodes for the pVII protein, which interacts and modulates virus DNA structure in the infected cells. The pVII protein is synthesized as the precursor protein and undergoes proteolytic processing by viral proteinase Avp, leading to release of a propeptide sequence and accumulation of the mature VII protein. Here we elucidate the molecular functions of the propeptide sequence present in the precursor pVII protein. The results show that the propeptide is the destabilizing element targeting the precursor pVII protein for proteasomal degradation. Our data further indicate that the propeptide sequence and the lysine residues K26 and K27 regulate the precursor pVII protein stability in a co-dependent manner. We also provide evidence that the Cullin-3 E3 ubiquitin ligase complex alters the precursor pVII protein stability by association with the propeptide sequence. In addition, we show that inactivation of the Cullin-3 protein activity reduces adenovirus E1A gene expression during early phase of virus infection. Collectively, our results indicate a novel function of the adenovirus propeptide sequence and involvement of Cullin-3 in adenovirus gene expression.
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| 2. |
- Locke Grandér, Barbara, et al.
(författare)
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Adapted tolerance to virus infections in four geographically distinct Varroa destructor-resistant honeybee populations
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The ectoparasitic mite, Varroa destructor, is unarguably the leading cause of honeybee (Apis mellifera) mortality worldwide through its role as a vector for lethal viruses, in particular, strains of the Deformed wing virus (DWV) and Acute bee paralysis virus (ABPV) complexes. Several honeybee populations across Europe have well-documented adaptations of mite-resistant traits but little is known about host adaptations towards the virus infections vectored by the mite. The aim of this study was to assess and compare the possible contribution of adapted virus tolerance and/or resistance to the enhanced survival of four well-documented mite-resistant honeybee populations from Norway, Sweden, The Netherlands and France, in relation to unselected mite-susceptible honeybees. Caged adult bees and laboratory reared larvae, from colonies of these four populations, were inoculated with DWV and ABPV in a series of feeding infection experiments, while control groups received virus-free food. Virus infections were monitored using RT-qPCR assays in individuals sampled over a time course. In both adults and larvae the DWV and ABPV infection dynamics were nearly identical in all groups, but all mite-resistant honeybee populations had significantly higher survival rates compared to the mite-susceptible honeybees. These results suggest that adapted virus tolerance is an important component of survival mechanisms.
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| 3. |
- Lukhovitskaya, Nina, et al.
(författare)
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A viral transcription factor exhibits antiviral RNA silencing suppression activity independent of its nuclear localization
- 2014
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 95, s. 2831-2837
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Tidskriftsartikel (refereegranskat)abstract
- Viral suppressors of RNA silencing (VSRs) are critical for the success of virus infection and efficient accumulation of virus progeny. The chrysanthemum virus B p12 protein acts as a transcription factor to regulate cell size and proliferation favourable for virus infection. Here, we showed that the p12 protein suppressed RNA silencing and was able to complement a VSR-deficient unrelated virus. Moreover, p12 counter-silencing activity could be uncoupled from its function as a transcription factor in the nucleus. The altered p12 protein, which lacked a nuclear localization signal and was not imported into the nucleus, was able to suppress RNA silencing as efficiently as the native protein. The data revealed new aspects of p12 functioning and identified a novel role for this viral zinc-finger transcription factor. The results provided a general insight into one of the activities of the p12 protein, which appeared to possess more than one function.
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| 4. |
- Lukhovitskaya, Nina, et al.
(författare)
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An RNA Virus-Encoded Zinc-Finger Protein Acts as a Plant Transcription Factor and Induces a Regulator of Cell Size and Proliferation in Two Tobacco Species
- 2013
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Ingår i: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 25, s. 960-973
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Tidskriftsartikel (refereegranskat)abstract
- Plant viruses cause a variety of diseases in susceptible hosts. The disease symptoms often include leaf malformations and other developmental abnormalities, suggesting that viruses can affect plant development. However, little is known about the mechanisms underlying virus interference with plant morphogenesis. Here, we show that a C-4 type zinc-finger (ZF) protein, p12, encoded by a carlavirus (chrysanthemum virus B) can induce cell proliferation, which results in hyperplasia and severe leaf malformation. We demonstrate that the p12 protein activates expression of a regulator of cell size and proliferation, designated upp-L (upregulated by p12), which encodes a transcription factor of the basic/helix-loop-helix family sufficient to cause hyperplasia. The induction of upp-L requires translocation of the p12 protein into the nucleus and ZF-dependent specific interaction with the conserved regulatory region in the upp-L promoter. Our results establish the role of the p12 protein in modulation of host cell morphogenesis. It is likely that other members of the conserved C-4 type ZF family of viral proteins instigate reprogramming of plant development by mimicking eukaryotic transcriptional activators.
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| 5. |
- Lukhovitskaya, Nina, et al.
(författare)
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Deciphering the Mechanism of Defective Interfering RNA (DI RNA) Biogenesis Reveals That a Viral Protein and the DI RNA Act Antagonistically in Virus Infection
- 2013
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 87, s. 6091-6103
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Tidskriftsartikel (refereegranskat)abstract
- Potato mop-top virus (PMTV) produces a defective RNA (D RNA) encompassing the 5'-terminal 479 nucleotides (nt) and 3'-terminal 372 nt of RNA-TGB (where TGB is triple gene block). The mechanism that controls D RNA biogenesis and the role of D RNA in virus accumulation was investigated by introducing deletions, insertions, and point mutations into the sequences of the open reading frames (ORFs) of TGB1 and the 8-kilodalton (8K) protein that were identified as required for efficient production of the D RNA. Transient expression of RNA-TGB in the absence of RNA-Rep (which encodes the replicase) did not result in accumulation of D RNA, indicating that its production is dependent on PMTV replication. The D RNA could be eliminated by disrupting a predicted minus-strand stem-loop structure comprising complementary sequences of the 5' TGB1 ORF and the 3' 8K ORF, suggesting intramolecular template switching during positive-strand synthesis as a mechanism for the D RNA biogenesis. Virus accumulation was reduced when the 8K ORF was disrupted but D RNA was produced. Conversely, the virus accumulated at higher titers when the 8K ORF was intact and D RNA production was blocked. These data demonstrate that the D RNA interferes with virus infection and therefore should be referred to as a defective interfering RNA (DI RNA). The 8K protein was shown to be a weak silencing suppressor. This study provides an example of the interplay between a pathogen and its molecular parasite where virus accumulation was differentially regulated by the 8K protein and DI RNA, indicating that they play antagonistic roles and suggesting a mechanism by which the virus can attenuate replication, decreasing viral load and thereby enhancing its efficiency as a parasite.
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| 6. |
- Thaduri, Srinivas, et al.
(författare)
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Disentangling host-parasite-pathogen interactions in a varroa-resistant honeybee population reveals virus tolerance as an independent, naturally adapted survival mechanism
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The ectoparasitic mite, Varroa destructor, is unarguably the leading cause of honeybee (Apis mellifera) mortality worldwide through its role as a vector for lethal viruses, in particular, strains of the Deformed wing virus (DWV) and Acute bee paralysis virus (ABPV) complexes. This multi-level system of host-parasite-pathogen interactions makes it difficult to investigate effects of either the mite or the virus on natural host survival. The aim of this study was to remove confounding effects of varroa to examine the role of virus susceptibility in the enhanced survival of a naturally adapted Swedish mite-resistant (MR) honeybee population, relative to mite-susceptible (MS) honeybees. Caged adult bees and laboratory reared larvae, from varroa-free colonies, were inoculated with DWV and ABPV in a series of feeding infection experiments, while control groups received virus-free food. Virus infections were monitored using RT-qPCR assays in individuals sampled over a time course. In both adults and larvae the DWV and ABPV infection dynamics were nearly identical between MR and MS groups, but MS adults suffered significantly higher mortality than MR adults. Results suggest virus tolerance, rather than reduced susceptibility or virus resistance, is an important component of the natural survival of this honeybee population.
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| 7. |
- Thaduri, Srinivas, et al.
(författare)
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Global similarity, and some key differences, in the metagenomes of Swedish varroa-surviving and varroa-susceptible honeybees
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing evidence that honeybees (Apis mellifera L.) can adapt naturally to survive Varroa destructor, the primary cause of colony mortality world-wide. Most of the adaptive traits of naturally varroa-surviving honeybees concern varroa reproduction. Here we investigate whether factors in the honeybee metagenome also contribute to this survival. The quantitative and qualitative composition of the bacterial and viral metagenome fluctuated greatly during the active season, but with little overall difference between varroa-surviving and varroa-susceptible colonies. The main exceptions were Bartonella apis and sacbrood virus, particularly during early spring and autumn. Bombella apis was also strongly associated with early and late season, though equally for all colonies. All three affect colony protein management and metabolism. Lake Sinai virus was more abundant in varroa-surviving colonies during the summer. Lake Sinai virus and deformed wing virus also showed a tendency towards seasonal genetic change, but without any distinction between varroa-surviving and varroa-susceptible colonies. Whether the changes in these taxa contribute to survival or reflect demographic differences between the colonies (or both) remains unclear.
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| 8. |
- Thaduri, Srinivas, et al.
(författare)
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Gut microbiota assembly of Gotland varroa-surviving honey bees excludes major viral pathogens
- 2023
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Ingår i: Microbiological Research. - 0944-5013 .- 1618-0623. ; 274
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Tidskriftsartikel (refereegranskat)abstract
- The spread of the parasite Varroa destructor and associated viruses has resulted in massive honey bee colony losses with considerable economic and ecological impact. The gut microbiota has a major role in shaping honey bees tolerance and resistance to parasite infestation and viral infection, but the contribution of viruses to the assembly of the host microbiota in the context of varroa resistance and susceptibility remains unclear. Here, we used a network approach including viral and bacterial nodes to characterize the impact of five viruses, Apis Rhabdovirus-1 (ARV-1), Black Queen Cell virus (BQCV), Lake Sinai virus (LSV), Sacbrood virus (SBV) and Deformed wing virus (DWV) on the gut microbiota assembly of varroa-susceptible and Gotland varroa-surviving honey bees. We found that microbiota assembly was different in varroa-surviving and varroa-susceptible honey bees with the network of the latter having a whole module not present in the network of the former. Four viruses, ARV-1, BQCV, LSV, and SBV, were tightly associated with bacterial nodes of the core microbiota of varroasusceptible honey bees, while only two viruses BQCV and LSV, appeared correlated with bacterial nodes in varroa-surviving honey bees. In silico removal of viral nodes caused major re-arrangement of microbial networks with changes in nodes centrality and significant reduction of the networks' robustness in varroa-susceptible, but not in varroa-surviving honey bees. Comparison of predicted functional pathways in bacterial communities using PICRUSt2 showed the superpathway for heme b biosynthesis from uroporphyrinogen-III and a pathway for arginine, proline, and ornithine interconversion as significantly increased in varroa-surviving honey bees. Notably, heme and its reduction products biliverdin and bilirubin have been reported as antiviral agents. These findings show that viral pathogens are differentially nested in the bacterial communities of varroa-surviving and varroa-susceptible honey bees. These results suggest that Gotland honey bees are associated with minimallyassembled and reduced bacterial communities that exclude viral pathogens and are resilient to viral nodes removal, which, together with the production of antiviral compounds, may explain the resiliency of Gotland honey bees to viral infections. In contrast, the intertwined virus-bacterium interactions in varroa-susceptible networks suggest that the complex assembly of microbial communities in this honey bee strain favor viral infections, which may explain viral persistence in this honey bee strain. Further understanding of protective mechanisms mediated by the microbiota could help developing novel ways to control devastating viral infections affecting honey bees worldwide.
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| 9. |
- Thaduri, Srinivas, et al.
(författare)
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Temporal changes in the viromes of Swedish Varroa-resistant and Varroa-susceptible honeybee populations
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The parasitic mite, Varroa destructor, in combination with the viruses it vectors, is the main cause for global colony losses of the European honeybee, Apis mellifera. However, an isolated honeybee population established in 1999 on the Island of Gotland, Sweden has naturally acquired resistance to the mite, and has survived without mite control treatment for more than 18 years. A recent study has shown that this mite resistant (MR) population also appears to be resistant to Black queen cell virus (BQCV) and Sacbrood virus (SBV) and tolerant to Deformed wing virus (DWV), relative to nearby mite susceptible (MS) honeybee populations. In this study, RNA sequencing was employed to corroborate these previous findings and identify other viral factors that may play a role in the enhanced survival of this mite resistant honeybee population. Two additional honeybee-infecting viruses, Apis rhabdovirus-1 (ARV-1) and Lake Sinai virus (LSV), were identified and near-complete genomes of these two viruses were obtained. Phylogenetic analyses of the assembled virus sequences revealed consistent separation between the MR and MS honeybee populations, although it is unclear whether this is due to pre-existing differences between the viruses in the two populations when they were established, and isolated, or due to virus genetic adaptation towards reduced virulence in the MR population, to promote colony survival. Reverse transcription quantitative polymerase chain reaction(RT-qPCR) analyses show higher ARV and LSV titres in MS colonies compared to MR colonies, gradually increasing from summer to autumn 2009, and reaching maximum titres in the following spring 2010. While the DWV and BQCV titres in MR colonies increased between autumn 2009 and spring 2010, the SBV practically disappeared entirely by spring 2010. Possible explanations for the apparent virus tolerance or resistance in the Gotland mite-resistant honeybee population are discussed.
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| 10. |
- Thaduri, Srinivas
(författare)
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Virus Dynamics in Naturally Varroa-Resistant Honeybee Populations
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ectoparasitic mite, Varroa destructor, together with its associated viruses is the most significant threat to honeybee (Apis mellifera) health world-wide. Since the introduction of varroa to the new host species, the European honey bee (Apis mellifera), it has been responsible for the near complete eradication of wild and feral honeybee populations in Europe and North America. However, a unique honeybee population on the island of Gotland, Sweden, has acquired resistance to the mite through a natural selection process. A recent study also showed that Gotland mite-resistant population might have adapted tolerance and resistance to virus infections. This suggests that virus-host interactions may play a key role in the long-term survival of this population. The aim of this thesis was to investigate the role of the viral and bacterial microbiome in the enhanced survival of the mite-resistant (MR) honeybees on Gotland, to compare the role of virus tolerance and resistance in other naturally selected mite-resistant honeybee populations, similar to the Gotland population, and to unravel individual level virus-host interactions in honeybees. First, by using a combination of high-throughput sequencing and different bioinformatics tools we found Lake Sinai virus and Apis rhabdovirus-1, including previously known honey bee viruses, in Swedish honey bees. Further molecular studies showed that Gotland MR bees have developed a colony-level resistance to these viruses, and tolerance to Deformed Wing Virus (DWV), the virus most commonly associated with mite infestation. Secondly, differences in the bacterial microbiome between MR and mite-susceptible (MS) bees were studied using the 16S rDNA, but the results indicated little differences between MR and MS bees throughout the season. Finally, individual level susceptibility of MR and MS honey bees to oral virus infection was tested for DWV virus and Acute bee paralysis virus (ABPV). The results demonstrate that DWV and ABPV infection dynamics were nearly identical in MR and MS bees, but that bees from the MR honeybee populations had significantly lower mortality rates than bees from the MS population. In conclusion, the results of this thesis present strong evidence that naturally adapted mite-resistant honeybees have also adapted, through a natural selection process, tolerance and resistance to virus infections at both the colony and individual level. The bacterial microbiome did not appear to play a role in the enhanced survival of Swedish mite-resistant honeybees but more studies are required to investigate potential bacteriavirus interactions on honeybee health. Future work should aim to identify key genomic regions associated with virus resistance and tolerance that can be incorporated into honeybee breeding programs to improve honeybee health.
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