Antiviral properties of bacteriophages: Can a bacteriophage infect other viruses?

Bacteriophages are viruses that are known to attack bacteria, their efficiency in eradicating the most antibiotic-resistant bacteria made scientists anxious to know the possibility of having bacteriophages that can help us fight pathogenic viruses. Some researches confirmed the existence of antiviral properties of bacteriophages to which if put in use phages can help to fight other viruses. 
different viruses
Different types of viruses


Do phages attack other viruses?

Bacteriophages do not attack other viruses, they are specific to the bacteria they attack. They use bacteria as a factory for their multiplication by attaching on bacterial surfaces and inject their genetic materials which will later result in the production of phage particles. I wrote an article on the possibility of bacteriophage infecting human cells which might enlighten you more on phage specificity.

How does a phage become an antiviral agent?

Instead of directly attacking other viruses, bacteriophages indirectly induce other mechanisms in the host body that may hinder the multiplication of other viruses. Most viruses depend on the host to multiply therefore if those systems are hindered the multiplication of the virus will be affected too.

Phage as a Potential Anti-Viral Agent

Downregulating NF-kappaB Activation

Viruses have evolved strategies to exploit NF kappa B signaling which is responsible for regulating gene expression involved in immune responses. This way helps viruses to avoid mechanisms that can clear them from the host body. in fact, the activation of NF kappa B signaling is a prerequisite for some viral infections. In contrast, phage does not cause significant activation of NF-kappa B in human endothelial and epithelial cells. Many researchers reported the ability of phages to prohibit the activation. Moreover, preincubation of these cells with phage abolishes (endothelium) or significantly reduces (epithelium) NF kappa B activation.

Lysogenic Conversion and Immune Response

Phage-dependent inhibition of NF-kappa B activity mentioned above was brought about by virulent phage. Furthermore, immunomodulatory effects reported by Van Belleghem et al. (2017) have also been mediated by such phage. On the other hand, phagicin production required induction of the lysogenic strain. No data are available on similar activities mediated by temperate phage. Interestingly, recent data from the Fischetti group have provided evidence that lysogeny plays a major role in the human adaptive immune response to bacterial infection. In those studies, prophages were shown to be responsible for a strong T and B cell immune response to lysogenic strains of bacteria (Sela et al., 2018). In contrast, lysogenic conversion has been shown to decrease phagocytosis of bacteria by phagocytes (Vaca-Pacheco et al., 1999; Secor et al., 2017). Thus, associations between lysogeny and immunity are complex and require further studies.

Phage Inhibit Adsorption and Replication of Human Adenovirus and Modify the Expression of Genes Involved in Antimicrobial Immunity

Adenoviruses
Human Adenovirus B7 courtey Relias Media


Studies on the effect of phage on stages of infection by a pathogenic virus, scientists found substantial dose-dependent inhibition by T4 phage of adsorption of HAdV to both A549 and HEK293 cell lines in vitro LPS was without effect. Moreover, T4 phage protected A549 cells from an HAdV-induced cytopathic effect (Międzybrodzki et al., 2013; Przybylski et al., 2015). These data suggest that T4 phage could be considered as a potential novel antiviral agent. The capacity of the phage to inhibit HAdV infection at the stage of viral replication suggests that phage could also interfere with viruses using cellular receptors other than those used by HAdV. Scientists observed the reduction of Adenoviral DNA synthesis when they incubated phage with adenovirus for a prolonged period although they suggest high titer is required to achieve early inhibition of HAdV gene expression while low titers will cause late inhibition
Borysowski et al., 2018 studied the effect of phages on the expression of genes involved in antimicrobial immunity by the A549 cell line from human lung, the most striking phenomenon was marked (>10-fold) enhancement of a gene coding for interleukin-2 (Il-2) by a staphylococcal phage. This effect is of particular interest in the context of the well-known role of NK cells in the immune response to viruses (Hammer et al., 2018) and the ability of Il-2 to induce those cells – even in ultra-low doses (Fehniger et al., 2000; Ito et al., 2014). Interestingly, a resident NK cell population is present in the human lung and may provide early and important control of viral infection (Cooper et al., 2018). Moreover, NK cells also exhibit activity against a variety of bacteria, e.g., by secretion of the soluble molecules perforin and granulysin. Mice infected with Shigella and lacking B and T cells but with normal NK cells have higher survival rates and lower bacterial titers than mice which lack all three cell types. This suggests that phage-induced Il-2 dependent activation of NK-mediated antimicrobial activity may contribute to beneficial effects of PT, especially during prolonged phage administration cumulative median duration of successful phage therapy is 43 days (Międzybrodzki et al., 2012). NK cells could be a promising agent in antimicrobial immunotherapy, as data strongly suggest that these cells are active against viral, bacterial, and fungal pathogens.

Bacteriophages are viruses that infect and kill bacterial cells. Several studies have confirmed that in addition to their antibacterial abilities, bacteriophages also show antiviral properties. The data presented in this article are extracted from different research publications. Don't forget to follow this blog for our future articles.

References
R. Międzybrodzki, W. Fortuna, B. Weber-Dąbrowska et al., “The in vitro studies on bacteriophage influence on the ability of human viruses to infect epithelial cells,” in Proceedings of the 20th Biennial Evergreen International Phage Meeting, Olympia, WA, USA, August 2013.
S. Trend, B. J. Chang, M. O’Dea, S. M. Stick, and A. Kicic, “Use of a primary epithelial cell screening tool to investigate phage therapy in cystic fibrosis,” Frontiers in Pharmacology, vol. 9, p. 1330, 2018.
Possible Role for Bacteriophages in the Treatment of SARS-CoV-2 Infection, Mishra et al, https://doi.org/10.1155/2020/8844963
Phage as an Antimicrobial Agent: D’herelle’s Heretical Theories and Their Role in the Decline of Phage Prophylaxis in the West Dottore Emiliano Fruciano and Shawna Bourne, https://doi.org/10.1155/2007/976850

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