The effects of dsRNA mycoviruses on growth and murine virulence of Aspergillus fumigatus

Bhatti, Muhammad Faraz; Jamal, Atif; Petrou, Michael F.; Cairns, Timothy C.; Bignell, Elaine; Coutts, Robert H.A.

doi:10.1016/j.fgb.2011.07.008

Cited by 72 publications

(83 citation statements)

References 28 publications

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“…To examine whether similarly purified dsRNAs from a negative control dsRNA fungal virus were uninfectious and that we were dealing with a previously unreported phenomenon with AfuTmV-1, we successfully transfected Af-237y protoplasts with AfuPV-1 virions but not a mixture of AfuPV-1 dsRNAs 1 and 2. Successful transfection of protoplasts with AfuPV-1 has been demonstrated previously (17), and this result was repeated here following positive RT-PCR amplification of the entire RdRP ORF on AfuPV-1 dsRNA 1 with no amplicons being produced in regenerated colonies transfected with a mixture of AfuPV-1 dsRNAs 1 and 2 ( Fig. S2A).…”

Section: Biological Comparison Of Virus-cured and Virus-infected Fungalsupporting

confidence: 78%

“…Strain NK125 is a virus-free strain obtained by cycloheximide treatment of strain Af293 as described by Bhatti et al (17), as verified by RT-PCR and northern hybridization analysis. Strain AF-237y is a virusfree, hygromycin-resistant yellow strain (17). A. fumigatus Δpaba is the mutated yellow strain (39) used as an avirulent control in the G. mellonella infectivity assays.…”

Section: Methodsmentioning

confidence: 99%

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A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA

Kanhayuwa

Kotta‐Loizou

Özkan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

122

226

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We report the discovery and characterization of a double-stranded RNA (dsRNA) mycovirus isolated from the human pathogenic fungus Aspergillus fumigatus, Aspergillus fumigatus tetramycovirus-1 (AfuTmV-1), which reveals several unique features not found previously in positive-strand RNA viruses, including the fact that it represents the first dsRNA (to our knowledge) that is not only infectious as a purified entity but also as a naked dsRNA. The AfuTmV-1 genome consists of four capped dsRNAs, the largest of which encodes an RNA-dependent RNA polymerase (RdRP) containing a unique GDNQ motif normally characteristic of negative-strand RNA viruses. The third largest dsRNA encodes an S-adenosyl methionine–dependent methyltransferase capping enzyme and the smallest dsRNA a P-A-S–rich protein that apparently coats but does not encapsidate the viral genome as visualized by atomic force microscopy. A combination of a capping enzyme with a picorna-like RdRP in the AfuTmV-1 genome is a striking case of chimerism and the first example (to our knowledge) of such a phenomenon. AfuTmV-1 appears to be intermediate between dsRNA and positive-strand ssRNA viruses, as well as between encapsidated and capsidless RNA viruses.

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Section: Biological Comparison Of Virus-cured and Virus-infected Fungalsupporting

confidence: 78%

Section: Methodsmentioning

confidence: 99%

A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA

Kanhayuwa

Kotta‐Loizou

Özkan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

122

226

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“…Second, Aspergillus fumigatus partitivirus 1 (AfuPV-1)-infected strain Af-237y-88 of Aspergillus fumigatus showed abnormal colony phenotypes, including slow growth, sectoring, and production of light pigmentation. However, any impact of AfuPV-1 on the virulence of its host is still unknown (45). Third, Rhizoctonia solani partitivirus 2 (RsPV2) was demonstrated to be associated with hypovirulence in Rhizoctonia solani AG-1IA (46).…”

Section: Discussionmentioning

confidence: 99%

A Novel Partitivirus That Confers Hypovirulence on Plant Pathogenic Fungi

Xiao

Chéng

Tang

et al. 2014

J Virol

128

103

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Members of the family Partitiviridae have bisegmented double-stranded RNA (dsRNA) genomes and are not generally known to cause obvious symptoms in their natural hosts. An unusual partitivirus, Sclerotinia sclerotiorum partitivirus 1 (SsPV1/WF-1), conferred hypovirulence on its natural plant-pathogenic fungal host, Sclerotinia sclerotiorum strain WF-1. Cellular organelles, including mitochondria, were severely damaged. Hypovirulence and associated traits of strain WF-1 and SsPV1/WF-1 were readily cotransmitted horizontally via hyphal contact to different vegetative compatibility groups of S. sclerotiorum and interspecifically to Sclerotinia nivalis and Sclerotinia minor. S. sclerotiorum strain 1980 transfected with purified SsPV1/WF-1 virions also exhibited hypovirulence and associated traits similar to those of strain WF-1. Moreover, introduction of purified SsPV1/WF-1 virions into strain KY-1 of Botrytis cinerea also resulted in reductions in virulence and mycelial growth and, unexpectedly, enhanced conidial production. However, virus infection suppressed hyphal growth of most germinating conidia of B. cinerea and was eventually lethal to infected hyphae, since very few new colonies could develop following germ tube formation. Taken together, our results support the conclusion that SsPV1/WF-1 causes hypovirulence in Sclerotinia spp. and B. cinerea. Cryo-EM (cryo-electron microscopy) reconstruction of the SsPV1 particle shows that it has a distinct structure with similarity to the closely related partitiviruses Fusarium poae virus 1 and Penicillium stoloniferum virus F. These findings provide new insights into partitivirus biological activities and clues about molecular interactions between partitiviruses and their hosts. IMPORTANCEMembers of the Partitiviridae are believed to occur commonly in their phytopathogenic fungal and plant hosts. However, most partitiviruses examined so far appear to be associated with latent infections. Here we report a partitivirus, SsPV1/WF-1, that was isolated from a hypovirulent strain of Sclerotinia sclerotiorum and describe its biological and molecular features. We have demonstrated that SsPV1 confers hypovirulence. Furthermore, SsPV1 can infect and cause hypovirulence in Botrytis cinerea. Our study also suggests that SsPV1 has a vigorous ability to proliferate and spread via hyphal contact. SsPV1 can overcome vegetative incompatibility barriers and can be transmitted horizontally among different vegetative compatibility groups of S. sclerotiorum, even interspecifically. Cryo-EM reconstruction of SsPV1 shows that it has a distinct structure with similarity to closely related partitiviruses. Our studies exploit a novel system, SsPV1 and its hosts, which can provide the means to explore the mechanisms by which partitiviruses interact with their hosts.

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“…Agents inducing stress or growth arrest have been used to cure fungal Totiviridae, with cycloheximide (CHX) used often (44,45). Growth of L. guyanensis at 10 or 100 nM CHX resulted in an increase in population doubling time, from ∼7.7 h to 11.2 or 44.7 h, respectively, without significant cell death as evidenced by resumption of WT growth following CHX removal (Fig.…”

Section: Lgylrv1mentioning

confidence: 99%

Antiviral screening identifies adenosine analogs targeting the endogenous dsRNALeishmaniaRNA virus 1 (LRV1) pathogenicity factor

Kuhlmann

Robinson

Bluemling

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The endogenous double-stranded RNA (dsRNA) virus Leishmaniavirus (LRV1) has been implicated as a pathogenicity factor for leishmaniasis in rodent models and human disease, and associated with drug-treatment failures in Leishmania braziliensis and Leishmania guyanensis infections. Thus, methods targeting LRV1 could have therapeutic benefit. Here we screened a panel of antivirals for parasite and LRV1 inhibition, focusing on nucleoside analogs to capitalize on the highly active salvage pathways of Leishmania, which are purine auxotrophs. Applying a capsid flow cytometry assay, we identified two 2′-C-methyladenosine analogs showing selective inhibition of LRV1. Treatment resulted in loss of LRV1 with first-order kinetics, as expected for random virus segregation, and elimination within six cell doublings, consistent with a measured LRV1 copy number of about 15. Viral loss was specific to antiviral nucleoside treatment and not induced by growth inhibitors, in contrast to fungal dsRNA viruses. Comparisons of drug-treated LRV1 + and LRV1 − lines recapitulated LRV1-dependent pathology and parasite replication in mouse infections, and cytokine secretion in macrophage infections. Agents targeting Totiviridae have not been described previously, nor are there many examples of inhibitors acting against dsRNA viruses more generally. The compounds identified here provide a key proof-ofprinciple in support of further studies identifying efficacious antivirals for use in in vivo studies of LRV1-mediated virulence.trypanosomatid protozoan parasite | endobiont virus | viral segregation | chemotherapy | virulence

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The effects of dsRNA mycoviruses on growth and murine virulence of Aspergillus fumigatus

Cited by 72 publications

References 28 publications

A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA

A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA

A Novel Partitivirus That Confers Hypovirulence on Plant Pathogenic Fungi

Antiviral screening identifies adenosine analogs targeting the endogenous dsRNALeishmaniaRNA virus 1 (LRV1) pathogenicity factor

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