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Viral interference originally was referred to a state of temporary immunity whereby infection with a virus limits replication of a second infecting virus. Importantly, replication of a second virus could also be dominant over the first virus. The effect of viral interference is revealed by well-known ...

Viral interference originally was referred to a state of temporary immunity whereby infection with a virus limits replication of a second infecting virus. Importantly, replication of a second virus could also be dominant over the first virus. The effect of viral interference is revealed by well-known epidemiologic and clinical observations. Different respiratory viruses reach their epidemic peaks at different times within populations. Progression to acquired immunodeficiency syndrome (AIDS) was slower in HIV infected patients who were coinfected with GB virus C and thus their survival was significantly longer than that of the patients with HIV monoinfections. Infection by one type of hepatitis virus (e.g. HCV) is often terminated after accidental coinfection by a second hepatitis virus (e.g. HBV). In persons with silent HBV and active HCV coinfection, HBV reactivation may occur following eradication of HCV by direct-acting antiviral (DAA) therapy. During viral interference expression of type I interferon genes is many times upregulated in infected cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific temporary state of immunity could be therapeutically exploited to provide a strategy to control viral infections.

While the COVID-19 pandemic reminded us to the destructive power of a viral infection, we should not forget that the billion-year evolutional interaction between cells and viruses resulted also in important mechanisms for innovation, e.g. viral interference. The feasibility of fighting fire with fire strategy, using non-pathogen viruses to control pathogen viruses, has already been validated by clinical studies. Controlled field trials involving more than 300 thousand people were carried out during three seasonal outbreaks of influenza and other associated acute respiratory infections with interferon-inducing live enteroviral vaccine (LEV) strains in the former Soviet Union. Administration of LEV provided protection and treatment against influenza and acute respiratory infections. Post-infection viral superinfection therapy (SIT), which administers an apathogenic attenuated live infectious bursal disease virus (IBDV) that delivers its double-stranded RNA (dsRNA) cargo to host cells, activates the antiviral interferon gene program of the host. SIT has been validated in close to 50 patients infected with either the hepatitis B (DNA) or hepatitis C (RNA) viruses. Preliminary evidence has been obtained about the safety and efficacy of SIT in COVID-19 patients. The goal of this collection therefore is to discuss the feasibility of post-infection approaches to control viral diseases by administering other non-pathogenic viruses.

This Research Topic will give a comprehensive overview about the impact of using non-pathogenic viruses to control viral diseases, with particular emphasis on the molecular mechanisms driving interferon induction and/or any other processes associated with response to therapy. The themes addressed by this Research Topic will include, but are not limited to, the followings:

• Immunological aspects and mechanism of viral coinfections
• Molecular mechanisms driving interferon induction in viral coinfections
• Clinically relevant natural viral coinfections (e.g., GBV-C/HIV; HBV/HCV and others)
• Reactivation of HBV following DAA therapy in HBV/HCV coinfections
• Therapeutic exploitation of viral interference
• Viral vaccines for the nonspecific therapy of respiratory diseases, including COVID-19 disease (e.g., live enterovirus and others)
• Attenuated virus treatment of COVID-19 disease (e.g., live IBDV, NDV and others)

We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.

Topic Editors Imre Kovesdi and Tibor Bakacs are shareholders of HepC, Inc. Topic Editor Imre Kovesdi is also a shareholder of DNAtrix, Inc. The other Topic Editors declare no competing interests.

Keywords: viral superinfection therapy, virus, infection


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