Fungal Virus Makes Ringworm Fungus More Virulent and Drug-Resistant

Mycoviruses, the viruses that infect fungi, have long been regarded as quiet passengers in the fungal world. Most of them persist without causing any visible change to their hosts, and many fungal species carry them for generations without any outward sign of infection. But a new study suggests that this quiet coexistence can be deceptive. Researchers have shown for the first time that a virus normally associated with a desert truffle can, when transferred into a human pathogenic fungus, dramatically change that fungus’s growth, its ability to cause disease, and its response to antifungal drugs. The findings, published in Virology Journal, come from a team led by Aysenur Simsek of Dokuz Eylul University in Izmir, Türkiye, working with collaborators across Turkish and Ukrainian institutions.

The fungus at the center of the study is Trichophyton rubrum, the dermatophyte most commonly responsible for ringworm and other superficial skin, hair, and nail infections in humans. Dermatophytes are among the most prevalent fungal pathogens worldwide, yet surprisingly little is known about whether they harbor mycoviruses and whether those viruses influence their behavior. To address this gap, the research team first screened clinical isolates of Trichophyton species for the presence of mycoviruses. They then turned to an experimental strategy that has rarely been applied to dermatophytes: heterologous transfection, the deliberate introduction of a virus from one host species into an entirely different one.

The virus chosen for the experiment was Terfezia claveryi endornavirus 1, abbreviated TcEV1, originally described in the desert truffle Terfezia claveryi. Endornaviruses form a distinctive group among mycoviruses. They possess double-stranded RNA genomes, lack the capacity to produce conventional virus particles, and are typically transmitted vertically through cell division and spores rather than spreading horizontally between individuals. Because of these properties, endornavirus infections are often described as cryptic, meaning they persist permanently within host lineages without producing virions or obvious symptoms. This cryptic lifestyle has made it difficult to assess what, if anything, endornaviruses do to their hosts, and has left open the question of whether they can jump between fungal species in nature or in the laboratory.

By introducing TcEV1 into T. rubrum through heterologous transfection, the researchers created a unique experimental system: a human pathogenic fungus carrying a viral passenger from a distant fungal lineage. The comparison between virus-free and virus-infected isolates of the same fungus allowed the team to isolate the specific effects of the virus from the background of the fungus’s own genetics. This controlled design is critical in mycovirus research, where differences between fungal strains can easily be mistaken for viral effects if the comparison is not carefully constructed.

The phenotypic consequences of TcEV1 infection were striking. Under laboratory conditions at 30 degrees Celsius, a temperature favorable to dermatophyte growth, the virus-infected isolate displayed increased radial growth compared with its virus-free counterpart. Radial growth rate is a standard measure of fungal fitness in vitro, reflecting how quickly a colony can expand across a substrate. The infected isolate also showed a significant rise in conidiation capacity, meaning it produced more conidia, the asexual spores through which dermatophytes spread from host to host and from lesion to lesion. Enhanced spore production could plausibly translate into greater transmissibility in a clinical setting, since the infectious dose of dermatophytes depends on the number of viable conidia shed by an infected individual.

The most consequential result, however, emerged from the in vivo experiments. Using a murine skin infection model, the researchers compared the ability of virus-free and TcEV1-infected T. rubrum to colonize living skin tissue. The virus-infected isolate achieved a fungal load approximately 2.5 times higher than the virus-free isolate. This roughly two-and-a-half-fold increase in fungal burden indicates that the presence of the endornavirus substantially enhanced the fungus’s capacity to establish and maintain infection in host tissue. The authors describe this as the first evidence of mycovirus-mediated enhanced virulence in T. rubrum, a finding that reframes mycoviruses from biological curiosities into potential modifiers of human disease severity.

Compounding the picture of heightened pathogenic potential, TcEV1 infection was also associated with reduced susceptibility to two major classes of antifungal agents: the echinocandins and amphotericin B. Echinocandins inhibit the synthesis of beta-glucan, a key structural component of the fungal cell wall, and are a mainstay of systemic antifungal therapy, while amphotericin B binds ergosterol in the fungal membrane and remains one of the most broadly active antifungal drugs available. A shift toward reduced susceptibility in a virus-carrying isolate suggests that mycoviral infection could complicate the treatment of dermatophytosis, although the study’s observations were made in vitro and the clinical implications for patients would require further investigation.

The mechanistic basis for these changes remains an open question. Endornaviruses encode RNA helicase motifs and other replication-associated proteins, and their persistent double-stranded RNA replicative form is a well-known trigger of antiviral responses in many host systems. In fungi, chronic viral infection can reshape metabolism, stress responses, and gene regulation in ways that alter growth and virulence. In plant-associated fungi, mycoviruses have been documented to attenuate virulence, as in the famous case of chestnut blight hypovirulence, but examples of mycoviruses increasing the pathogenicity of a human fungal pathogen are exceedingly rare. The T. rubrum system therefore offers a valuable platform for dissecting how a persistent RNA virus reprograms a dermatophyte’s physiology, from cell wall architecture to spore development and interaction with host tissue.

The study also carries broader implications for how mycologists and clinicians think about fungal disease. If cross-species transmission of mycoviruses can convert a cryptic infection into a driver of enhanced virulence and drug tolerance, then the viral status of clinically important fungi becomes a variable worth monitoring. Screening for mycoviruses could one day complement conventional susceptibility testing, particularly for isolates that behave unusually in the clinic. The finding that an endornavirus from a truffle-associated fungus can establish itself in a dermatophyte also hints that the boundaries between mycoviral host ranges may be more permeable than previously assumed, raising the possibility that such transfers occur in natural settings where fungi share environments.

The research originated from the master’s thesis of Aysenur Simsek at Dokuz Eylul University’s Institute of Science and was supported by the Scientific and Technological Research Council of Türkiye under project number 122Z630 and by Dokuz Eylul University under project number FYL-2025-3680. The corresponding authors are Tetiana Krupodorova of the National Academy of Sciences of Ukraine in Kyiv and Ergin Sahin of Dokuz Eylul University. As the first demonstration that heterologous transfection of an endornavirus can enhance the virulence of a major human dermatophyte both in culture and in a living host, the work opens a new chapter in the study of fungal viruses, one in which the invisible RNA passengers of fungi may help determine how aggressively those fungi infect us and how well our drugs work against them.

Subject of Research: Mycovirus-mediated enhancement of virulence and antifungal resistance in the dermatophyte Trichophyton rubrum

Article Title: Heterologous transfection of an endornavirus alters the phenotype of Trichophyton rubrum in vitro and in vivo

Article References: Simsek, A., Ozturk, N., Akata, I., Batir, M. B., Kaya, S., Kaya, E., Krupodorova, T., Sevindik, M., Edis, G., & Sahin, E. (2026). Heterologous transfection of an endornavirus alters the phenotype of Trichophyton rubrum in vitro and in vivo. Virology Journal. https://doi.org/10.1186/s12985-026-03295-y

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03295-y

Keywords: mycovirus, endornavirus, Trichophyton rubrum, dermatophytosis, TcEV1, heterologous transfection, virulence, antifungal resistance, echinocandins, amphotericin B, murine infection model, double-stranded RNA