Epstein–Barr virus and mechanisms of molecular carcinogenesis

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Abstract

Epstein–Barr virus (EBV) is widespread among the human population and underlies development of numerous malignant neoplasms. The mechanism of EBV-associated carcinogenesis is based on the ability of viral proteins and microRNAs to cause genetic and epigenetic changes which can directly or indirectly stimulate cell growth, inhibit apoptosis, and protect tumor cells from the effects of their microenvironment and the host’s immune response. EBV can lead to development of such malignant neoplasms as Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal, gastric cancer, etc. The review discusses molecular mechanisms of EBV-associated carcinogenesis promoting the virus’s survival in the host’s cells, and regulating oncoproteins.

The results of more than 500 studies from the PubMed, Google Scholar, ResearchGate, Web of Science, RSCI (Russian Science Citation Index) and CyberLeninka databases performed primarily in the last 10 years were analyzed. Literature analysis has shown that EBV has a wide variety of mechanisms to avoid immune surveillance which ensures its lifelong persistence in the human body. Expression of latent proteins (in particular, EBNA1, LMP1, and LMP2A) which modulate the host’s signaling pathways, suppress apoptosis, and alter the immune response, plays the key role in its survival. Additionally, it was established that the type of latency maintained in the infected cells affects the probability of malignant transformation. For example, type II latency is characteristic of the majority of epithelial tumors, while type III is associated with lymphomas. Transition from latent to lytic phase is accompanied by expression of proteins promoting carcinogenesis. In the literature, special attention is paid to the roles of LMP1 and LMP2A oncoproteins which activate PI3K/AKT and JAK/STAT pathways disturbing regulation of cell proliferation and apoptosis. EBV-induced tumors are often characterized by epigenetic changes supporting persistence of the virus and tumor cell growth.

Therefore, EBV is capable of extorting multifactorial effects on the host cell which makes it an important subject of cancer virology. This confirms the necessity of further studies for refinement of molecular mechanisms of carcinogenesis and development of targeted therapeutic approaches to treatment of EBV-associated tumors.

About the authors

A. D. Molchanov

N.N. Blokhin National Medical Research Center of Oncology; Sechenov University, Ministry of Health of Russia

Author for correspondence.
Email: m.artem.aug@gmail.com
ORCID iD: 0000-0001-5229-2285

Artem Dmitrievich Molchanov

24 Kashirskoe Shosse, Moscow 115522

Bld. 2, 8 Trubetskaya St., Moscow 119991

Russian Federation

A. S. Vasilyeva

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0009-0004-0249-4574

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

K. V. Smirnova

N.N. Blokhin National Medical Research Center of Oncology

Email: fake@neicon.ru
ORCID iD: 0000-0001-6209-977X

24 Kashirskoe Shosse, Moscow 115522

Russian Federation

M. V. Nemtsova

Sechenov University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-2835-5992

Bld. 2, 8 Trubetskaya St., Moscow 119991

Russian Federation

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