24 Aug Hebrew University Study Finds Fungus Contains Mycovirus That Makes Infections More Virulent and Difficult to Treat

MedicalResearch.com Interview with:

Dr. Neta Shlezinger | Credit: Zuckerman Faculty Scholar Zuckerman Institute

Dr. Neta Shlezinger Ph.D.
Koret School of Veterinary Medicine
Hebrew University

with  Dr. Marina Campos Rocha Ph.D., Dr. Vanda Lerer, PhD., and student John Adeoye

MedicalResearch.com: What is the background for this study?  What are the main findings?

Response:  Fungal pathogens pose a growing threat to global health, particularly for immunocompromised individuals. Today, we appreciate that fungi kill more people each year than malaria and tuberculosis combined. Aspergillus fumigatus stands out as a leading cause of invasive fungal infections, responsible for approximately 65% of all invasive mold infections in humans.

These infections carry mortality rates that can exceed 50%, even with standard care. Treatment options remain limited: only a handful of antifungal drug classes are clinically available, and resistance is increasingly reported to all of them. As a result, the search for novel therapeutic strategies is now focused on fungal-specific virulence factors — targets that are essential for fungal survival and pathogenicity in the host but are absent in humans.

Meanwhile, research in recent years has revealed that many fungi harbor viruses. These mycoviruses are surprisingly prevalent, but their impact on fungal physiology and, crucially, on fungal pathogenicity in humans has remained largely unexplored.

Our study set out to fill this gap by examining a double-stranded RNA virus, Aspergillus fumigatus polymycovirus 1 (AfuPmV-1M), that naturally infects A. fumigatus. We found that this virus isn’t just a silent passenger — it’s wired into key fungal stress response pathways, helping the fungus survive heat stress, evade oxidative damage, and persist in the lung environment. In other words, it acts like a backseat driver — quietly steering the fungus toward enhanced survival and virulence.

When we “cured” the fungus of its virus, it produced fewer spores, made less melanin, became more vulnerable to stress, and caused milder infections in mice. Seeing this, we explored a therapeutic twist: fight the virus to clear the fungus.

We treated infected mice with antiviral compounds during fungal infection and observed reduced mycovirus levels and improved survival.

Together, these results suggest that mycoviruses can be overlooked drivers of fungal disease — and targeting them may represent a novel, host-sparing therapeutic strategy.

MedicalResearch.com:  Does this mycovirus cause disease on its own as well? Does it infect other fungi?

Response: To our knowledge, AfuPmV-1M or other mycoviruses cannot replicate in mammalian cells, nor is there evidence that it can cause disease independently of its fungal host. That said, fungal spores are readily phagocytosed by immune cells, and intracellular persistence creates a theoretical opportunity — albeit remote — for viral adaptation to mammalian cellular machinery. While this scenario is speculative, it warrants consideration in the context of long-term host-pathogen evolution.

As for the host range, related polymycoviruses have been identified in a variety of fungi, including entomopathogenic and environmental species. However, mycoviruses are unique in their lack of an extracellular phase — they are transmitted vertically through spores or horizontally via hyphal fusion. This raises fascinating questions about their transmission potential across fungal species, which remains poorly understood due to the protective nature of the fungal cell wall and the absence of a canonical virion stage. Understanding these dynamics could have implications for fungal ecology, pathogenesis, and interspecies viral exchange.

MedicalResearch.com: What should readers take away from your report?

Response: Our findings challenge the conventional view that fungal virulence is shaped solely by the fungus itself or by host immunity. Sometimes, the real driver is a hidden passenger.

Mycoviruses like AfuPmV-1M may look like harmless hitchhikers, but in reality, they can act as backseat drivers — subtly, yet powerfully, steering the course of infection. In this case, the virus is hardwired into A. fumigatus’s stress response circuitry, helping the fungus survive heat, oxidative bursts, and the hostile environment of the host lung.

So perhaps the next time someone presents with a fungal infection, the question shouldn’t just be “Which fungus?” — but also “Is it carrying a virus?”

And this raises deeper questions: Are we really looking at two separate entities — a fungus and a virus? Or should we consider the virus-infected fungus as a new, unified entity — a kind of pathogenic chimera whose virulence emerges from the intimate alliance of both? In understanding infectious disease, we may need to broaden our lens — not just to isolate contributing factors, but to recognize when pathogenicity emerges from the inseparable partnership between them. 

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: This study is likely just the tip of the iceberg. The fungal virome remains vastly underexplored — and we now have reason to believe that its effects on fungal fitness, stress tolerance, and pathogenicity may be profound.

We recommend expanding investigations to other fungal pathogens and their associated viruses, where different interactions may yield diverse outcomes. Some mycoviruses may attenuate virulence; others, like AfuPmV-1M, may enhance it. Understanding these dynamics at a molecular level will be key to identifying novel targets for antifungal therapy.

We also urge further exploration of antiviral interventions — either as standalone therapies or as adjuncts to traditional antifungal drugs — particularly in settings of drug resistance or immune dysfunction.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: This work underscores a broader paradigm shift: we may need to think of mycovirus-carrying fungi not as two discrete biological entities, but as a single, co-evolved infectious unit. The virus and its fungal host are locked in a mutualistic relationship — and that partnership directly influences human disease.

Disclosures: No relevant financial conflicts of interest are declared. This work was supported by the European Research Council (ERC) Starting Grant MycoViralPath (Grant Number 101077734).

Citation:

Rocha, M.C., Lerer, V., Adeoye, J. et al. Aspergillus fumigatus dsRNA virus promotes fungal fitness and pathogenicity in the mammalian host. Nat Microbiol (2025). https://doi.org/10.1038/s41564-025-02096-3

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Last Updated on August 24, 2025 by Marie Benz MD FAAD