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. The knowledge in antiviral properties of the bacteriophages is still limited, despite the effort made by scientists (Don't confuse bacteriophages and Virophages). Virophages are viral particles known to infect viruses while bacteriophages (as I may term as phages in this article) are the entities known to infect bacteria.
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 injecting 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. Viruses have their own specific phages called Virophages as introduced above. There are only a few of them that have so far been reported in the science world making the least prevalent type of phages.

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. Some studies have suggested the direct induced effect to the virus without involving the host interaction, meaning that the effect of bacteriophage on a virus can be felt both in vivo and in vitro. In most of the latter methods, phages will depend on the availability of a certain receptor on the surface of the virus in question.

Phage as a Potential Anti-Viral Agent

The following discussion on the potentiality of phages having antiviral properties was extracted from information provided by different peer-reviewed published researches as the information references will be declared.

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

Many people think of lytic phages to be the only ones to be considered when it comes to phage application, although that might not be true due to some reasons. Unlike lytic phages, Lysogenic phages are responsible for inducing phagicin production, Phagicin is an antiviral protein in nature. Adding to that, recent data from the Fischetti group have provided evidence that lysogeny plays a major role in the human adaptive immune response to bacterial infection. This revealed information is opening the door for more researches to be done on lysogenic phages. A study done by Sela et al. (2018) suggests that prophages are responsible for a strong T and B cell immune response. In contrast, lysogenic conversion has been shown to decrease phagocytosis of bacteria by phagocytes bringing the negative bits of using lysogenic phages. 

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

Adenoviruses
Human Adenovirus B7 courtesy Relias Media


When it comes to phages, scientists have so far done a lot in a race to understand the full capability of these particles. Studies on the effect of phage on stages of infection by a pathogenic virus have been done and the results were outstanding. They found a substantial dose-dependent inhibition by T4 phage on the adsorption of Human adenovirus (HAdV) to cell lines in vitro LPS was without effect. Moreover, Międzybrodzki et al. (2013) observed T4 phage-protected cells from an HAdV-induced cytopathic effect. These data suggest that T4 phage could be considered as a potential novel antiviral agent although more studies are needed on proving the practicality of this. 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 caused late inhibition.

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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