The Fight against the Carcinogenic Epstein-Barr Virus: Gut Microbiota, Natural Medicines, and Beyond

Abstract

Despite recent advances in oncology, cancer has remained an enormous global health burden, accounting for about 10 million deaths in 2020. A third of the cancer cases in developing counties are caused by microbial infections such as human papillomavirus (HPV), Epstein-Barr Virus (EBV), and hepatitis B and C viruses. EBV, a member of the human gamma herpesvirus family, is a double-stranded DNA virus and the primary cause of infectious mononucleosis. Most EBV infections cause no long-term complications. However, it was reported that EBV infection is responsible for around 200,000 malignancies worldwide every year. Currently, there are no vaccines or antiviral drugs for the prophylaxis or treatment of EBV infection. Recently, the gut microbiota has been investigated for its pivotal roles in pathogen protection and regulating metabolic, endocrine, and immune functions. Several studies have investigated the efficacy of antiviral agents, gut microbial metabolites, and natural products against EBV infection. In this review, we aim to summarise and analyse the reported molecular mechanistic and clinical studies on the activities of gut microbial metabolites and natural medicines against carcinogenic viruses, with a particular emphasis on EBV. Gut microbial metabolites such as short-chain fatty acids were reported to activate the EBV lytic cycle, while bacteriocins, produced by Enterococcus durans strains, have shown antiviral properties. Furthermore, several natural products and dietary bioactive compounds, such as curcumin, epigallocatechin gallate, resveratrol, moronic acid, and andrographolide, have shown antiviral activity against EBV. In this review, we proposed several exciting future directions for research on carcinogenic viruses.

The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment

“…EBV is a herpesvirus (officially known as Human Gamma herpesvirus 4) commonly transmitted through bodily fluids such as saliva and is the primary cause of infectious mononucleosis (IM), but is also associated with other illnesses, such as certain types of lymphoma and nasopharyngeal carcinoma. EBV is one of the most prevalent human viruses, infecting around 95% of the population, and no particular therapy or vaccination is available [28]. Primary EBV infection in childhood is usually asymptomatic; nevertheless, when infection occurs later in life, the virus can cause IM in 35-50% of instances [29].…”

“…Primary EBV infection in childhood is usually asymptomatic; nevertheless, when infection occurs later in life, the virus can cause IM in 35-50% of instances [29]. Human T-lymphotropic virus 1 (HTLV-1) is primarily transmitted through blood transfusions, sharing needles, and from mother to child during childbirth or breastfeeding, and chronic infection with HTLV-1 can led to a rare type of leukemia and a neurological condition called HAM/TSP [28].…”

“…Virus-mediated carcinogenesis involves a series of sequential steps that transform normal cells into cancer cells. These steps-initiation, promotion, and progression-have been extensively studied and documented [28,30]. During the initiation phase, a carcinogen interacts with the host DNA, setting the groundwork for subsequent cellular changes.…”

“…It is important to note that viral infections can increase the susceptibility of our DNA to mutations. For instance, the viral antigen EBNA-1 derived from the Epstein-Barr virus (EBV) has been found to induce genomic instability by activating RAG1 and RAG2 [25,28]. EBV has been associated with various cancers, including Burkitt lymphoma (BL), Hodgkin disease, nasopharyngeal carcinoma (NPC), gastric cancer, T/NK lymphoma (nasal natural killer/T-cell lymphoma), as well as AIDSor transplantation-associated lymphomas [33].…”

“…EBV has been associated with various cancers, including Burkitt lymphoma (BL), Hodgkin disease, nasopharyngeal carcinoma (NPC), gastric cancer, T/NK lymphoma (nasal natural killer/T-cell lymphoma), as well as AIDSor transplantation-associated lymphomas [33]. While conventional antiviral drugs like acyclovir and ganciclovir have demonstrated the ability to inhibit EBV lytic replication in laboratory settings, none have received FDA approval thus far [28,29] Furthermore, numerous antiviral treatments tested in clinical trials have proven ineffective [34]. As a result, there is a pressing need to develop innovative, effective, and safe antiviral medications targeting EBV and BL.…”