Cell-Cell Fusion Mediated by Viruses and HERV-Derived Fusogens in Cancer Initiation and Progression

Abstract

Cell fusion is a well-known, but still scarcely understood biological phenomenon, which might play a role in cancer initiation, progression and formation of metastases. Although the merging of two (cancer) cells appears simple, the entire process is highly complex, energy-dependent and tightly regulated. Among cell fusion-inducing and -regulating factors, so-called fusogens have been identified as a specific type of proteins that are indispensable for overcoming fusion-associated energetic barriers and final merging of plasma membranes. About 8% of the human genome is of retroviral origin and some well-known fusogens, such as syncytin-1, are expressed by human (cancer) cells. Likewise, enveloped viruses can enable and facilitate cell fusion due to evolutionarily optimized fusogens, and are also capable to induce bi- and multinucleation underlining their fusion capacity. Moreover, multinucleated giant cancer cells have been found in tumors derived from oncogenic viruses. Accordingly, a potential correlation between viruses and fusogens of human endogenous retroviral origin in cancer cell fusion will be summarized in this review.

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

“…In our previous work, we elaborated on the connection between the SARS-CoV-2 virus and cellular senescence, a subject that will not be discussed in detail here, however, as senescence was associated with microtubular reorganization, the virus may contribute to neurodegeneration by promoting Tau hyperphosphorylation ( Ramani et al., 2020 ; Sfera et al., 2021 ; Sfera et al., 2021 ; Pratt et al., 2021 ) Indeed, pTau, genome destabilization, and HERV activation, may promote neurotoxic astrocytes and microglia, phenomena previously linked to neuronal and synaptic loss ( Hornik et al., 2014 ; Brelstaff et al., 2018 ; Dittmar et al., 2021 ; Sokolova et al., 2021 ). In addition, our focus will be on the cell-cell fusion with less emphasis on virus-host merger, a topic that exceeds the purpose of this review.…”

COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

“…FCS was reported to activate HERVs, primarily type W and K, triggering not only cell-cell fusion but also hyperinflammatory responses and dysfunctional proteostasis [114][115][116][117]. HERVs are viral fossils embedded in human DNA that can be "awakened" by the infection with exogenous viruses, cancer, or neuropsychiatric conditions [118][119][120].…”

Alternative and aberrant splicing of human endogenous retroviruses in cancer. What about head and neck? —A mini review

“…As abovementioned, the well-conserved env genes from HERV-W1 and HERV- FRD transcribe for Syncytin-1 and Synicitin-2, respectively, and mediate the fusion of villous cytotrophoblasts during placentation ( 99 , 100 ). In fact, Env protein has fusogenic properties and has been proposed to have a role in cancer, including in epithelial-to-mesenchymal transition ( 101 , 102 ).…”