Mycovirus Containing Aspergillus flavus and Acute Lymphoblastic Leukemia: Carcinogenesis beyond Mycotoxin Production

Abstract

Carcinogenic effects of Aspergillus spp. have been well established and generally attributed to a variety of mycotoxin productions, particularly aflatoxins. It is known that most carcinogenic mycotoxins, with the exception of fumonisins, are genotoxic and mutagenic, causing chromosomal aberrations, micronuclei, DNA single-strand breaks, sister chromatid exchange, unscheduled DNA synthesis etc. Some Aspergillus spp. are infected with mycoviruses which can result in loss of aflatoxin production. The effects of mycovirus containing Aspergillus on human health have not been fully evaluated. Recent studies in patients with acute lymphoblastic leukemia, in full remission, have revealed the existence of antibody to the products of a certain Aspergillus flavus isolate which harbored an unknown mycovirus. Exposure of blood mononuclear cells from these patients, but not controls, to the products of this organism had reproduced cell surface phenotypes and genetic markers, characteristic of acute lymphoblastic leukemia. Carcinogenic effects of Aspergillus spp. may not always be mycotoxin related and this requires further investigation.

Inseparable companions: Fungal viruses as regulators of fungal fitness and host adaptation

“…Given the commonalities between known oncogenes and viral-targeted cellular pathways, it is not surprising that some mammalian viruses can cause cancer by circumventing or hijacking cell death modalities. Interestingly, a recent study discovered that plasma from lymphoblastic leukemia (ALL) patients, was reactive with supernatants from a mycovirus-containing Aspergillus flavus isolate, while sera from healthy controls were non-reactive, suggesting mycovirus-mediated leukemogenesis in this group of patients ( Tebbi et al., 2021 ). The question arises, whether mycoviruses may impact human or animal health directly or once internalized using the fungal cell as a carrier.…”

Mycoviruses in Fungi: Carcinogenesis of Fungal Agents May Not Always Be Mycotoxin Related

“…Several studies have correlated the possible involvement and association of fungal species, particularly Candida , with the development and progression of various types of cancer. While most attention has been directed to yeasts in the so-called blastomycete theory of cancer, more recently, other mechanisms, including the possible role of mycoviruses in fungal organisms, have been suggested [ 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ]. In the recent past, it has been shown that the in vitro exposure of mononuclear cells from individuals who have a history of acute lymphoblastic leukemia (ALL) and are in full remission, without any evidence of the disease, including long-term survivors, to a certain mycovirus-containing Aspergillus flavus (MCAF) results in the re-development of cell surface phenotypes and genetic markers characteristic of active ALL [ 91 ].…”

“…If this is due to the certain genetic or epigenetic background in the ALL patients is not clear. In a related study, unlike controls, patients with ALL were found to have antibodies for the products of MCAF [ 92 ]. It is of interest that the mycovirus-containing Aspergillus flavus used for these studies was isolated from the home of a patient with ALL and the organism did not produce any aflatoxin [ 91 , 92 ].…”

“…In a related study, unlike controls, patients with ALL were found to have antibodies for the products of MCAF [ 92 ]. It is of interest that the mycovirus-containing Aspergillus flavus used for these studies was isolated from the home of a patient with ALL and the organism did not produce any aflatoxin [ 91 , 92 ]. A well-known theory for the etiology of ALL in the pediatric age group suggests that the development of this disease is due to a combination of genetic mutations and exposure to infections [ 100 ].…”

“…It is suggested that the risk can be further modified by other inherited genetics, and possibly diet, as well as chance. While a number of predisposing genetic factors have been identified, until recent reports [ 91 , 92 ], no certain infectious agents had been proposed. Based on the recent findings, it is postulated that exposure to mycovirus-containing Aspergillus flavus could possibly be one of the post-natal infections that can trigger the second step in the developmental process of ALL [ 91 ].…”