Awakening the sleeping giant: Epstein–Barr virus reactivation by biological agents, 2024, Omkar Indari et al

[Mij]

Abstract​

Epstein–Barr virus (EBV) may cause harm in immunocompromised conditions or on stress stimuli. Various chemical agents have been utilized to induce the lytic cycle in EBV-infected cells. However, apart from chemical agents and external stress stimuli, certain infectious agents may reactivate the EBV. In addition, the acute infection of other pathogens may provide suitable conditions for EBV to thrive more and planting the roots for EBV-associated pathologies.

Various bacteria such as periodontal pathogens like Aggregatibacter, Helicobacter pylori, etc. have shown to induce EBV reactivation either by triggering host cells directly or indirectly. Viruses such as Human simplex virus-1 (HSV) induce EBV reactivation by HSV US3 kinase while other viruses such as HIV, hepatitis virus, and even novel SARS-CoV-2 have also been reported to cause EBV reactivation. The eukaryotic pathogens such as Plasmodium falciparum and Aspergillus flavus can also reactivate EBV either by surface protein interaction or as an impact of aflatoxin, respectively. To highlight the underexplored niche of EBV reactivation by biological agents, we have comprehensively presented the related information in this review.

This may help to shedding the light on the research gaps as well as to unveil yet unexplored mechanisms of EBV reactivation.
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[Mij]

Conclusion​

EBV reactivation is one of the pivotal steps in developing any EBV-associated complications such as cancer. Many types of biological agents, including bacteria, viruses, fungi, and protozoa have been reported to reactivate EBV. In one way, some of these biological entities can either directly interact with EBV-infected cells to drive the EBV reactivation as seen in the case of Pl. falciparum-driven BCR stimulation and EBV reactivation (Fig. 4).

In another way, the biological agents can modulate nearby microenvironments or produce molecules that may stimulate the cell for EBV lytic cycle progression as seen in the case of Helicobacter pylori, periodontal pathogens, Aspergillus flavus, etc. Most of the viruses can drive the process from inside the cells to activate lytic gene promotors as observed in the case of HSV-1 and HHV6.

We also additionally have shown here the host proteins interacting with SARS-CoV-2 protein and having a potential role in EBV reactivation. This information would be important for gaining additional insight into SARS-CoV-2-mediated EBV reactivation by further research. There is indeed an increased need to avail the details of biological agents causing EBV reactivation as the main cause of observed complications may stay hidden.

The original culprit of EBV-associated complications could actually be some other biological agents as observed in case of the development of Burkitt’s lymphoma post malaria-mediated EBV reactivation. Future research will help in understanding the interplay of pathogens playing role in EBV reactivation. It may aid in developing therapeutic interventions to minimize the complications associated with such scenarios.