Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities

Abstract

Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.

Keywords: Antiviral Agents; Malignancy; Oncoviruses; Therapeutics; Viral Oncogenesis.

Figure 1

Various oncogenic viral strains have taken various pathways to infect the host organism, leading to cancerous proliferation (Created in Biorender).

Figure 2

Pro-oncogenic inflammatory microenvironment induced by HCV. HCV infection in hepatocytes is detected by viral sensors, such as RIG-I and TLR3, leading to the production of type I IFNs. As with most viruses, HCV has developed various strategies to dampen this antiviral response. The persistent inflammatory environment in the liver, combined with the action of viral proteins, establishes a sustained activation of signaling pathways associated with cell survival (e.g., STAT3, AKT, NF-κB, and FasR). Sensing HCV-infected hepatocytes by macrophages triggers NLRP3 inflammasomes, inducing the secretion of IL-18, which activates NK cells. Moreover, IL-1b and IL-6 produced by macrophages favor the activation of HSCs which are central components in the progressive deposition of collagen associated with liver cirrhosis. STAT3 also plays a role in developing MDSCs, which produce IL-10 and favor the expansion of regulatory T cells. This altered immune response is further accentuated by the increased expression of PD-1 and FasL, impairing cytotoxic T lymphocyte function and inducing their apoptosis (adapted with permission under a creative commons (CC-BY 4.0) from ref (124)). Copyright [2020] [MDPI].

Figure 3

Schematic representation of the lymphoma microenvironment including immune components (CD4 and CDT lymphocytes, macrophages, cytokines, and chemokines) and nonimmune components (fibroblasts, stromal cells, and blood vessels). This figure includes viruses and their products influencing the microenvironment (Created in Biorender).

Figure 4

Different antiviral agents to curb the action of oncogenic viruses on the molecular front (Created by Biorender).