Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Oct 27:13:1059133.
doi: 10.3389/fimmu.2022.1059133. eCollection 2022.

EBV-associated diseases: Current therapeutics and emerging technologies

Srishti Chakravorty  1 , Behdad Afzali  2 , Majid Kazemian  1   3
Affiliations
Review

EBV-associated diseases: Current therapeutics and emerging technologies

Srishti Chakravorty et al. Front Immunol. .

Abstract

EBV is a prevalent virus, infecting >90% of the world's population. This is an oncogenic virus that causes ~200,000 cancer-related deaths annually. It is, in addition, a significant contributor to the burden of autoimmune diseases. Thus, EBV represents a significant public health burden. Upon infection, EBV remains dormant in host cells for long periods of time. However, the presence or episodic reactivation of the virus increases the risk of transforming healthy cells to malignant cells that routinely escape host immune surveillance or of producing pathogenic autoantibodies. Cancers caused by EBV display distinct molecular behaviors compared to those of the same tissue type that are not caused by EBV, presenting opportunities for targeted treatments. Despite some encouraging results from exploration of vaccines, antiviral agents and immune- and cell-based treatments, the efficacy and safety of most therapeutics remain unclear. Here, we provide an up-to-date review focusing on underlying immune and environmental mechanisms, current therapeutics and vaccines, animal models and emerging technologies to study EBV-associated diseases that may help provide insights for the development of novel effective treatments.

Keywords: EBV animal models; EBV therapeutics; EBV vaccines; EBV-associated diseases and cancers; high-throughput sequencing technologies; molecular mechanisms of EBV-host interactions.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Model of EBV infection cycle. (A) Upon primary infection through saliva, EBV infects B cells. The figure depicts a model of EBV infection, where in EBV drives naïve B cells into latency III program. This activation leads to their differentiation into latency I/O memory B cells. This is often followed by spontaneous or induced reactivation of EBV within circulating memory B cells. This figure is adapted/modified from Guo et al (44). (B) Depending on the type of latency or lytic program, EBV infected cells are associated with different malignancies.*Gastric cancer cells also express genes that are associated with latency II programs. **Post-transplant lymphoproliferative disorders express some of the genes in latency III as well.
Figure 2
Figure 2
A few examples of key host cellular processes perturbed by EBV. Examples of EBV-encoded gene products that are related to the indicated mechanism are shown.
Figure 3
Figure 3
Therapeutic approaches hypothesized or in clinical use, for the treatment of EBV-associated malignancies. Shown are broad categories of treatments (red), subcategories (bold) and specific examples (italicized). HDAC: Histone deacetylase; DNMT: DNA methyltransferase; R-CHOP: Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.
Figure 4
Figure 4
Ltic induction or cytolytic virus activation therapy (CLVA). CLVA can make latently infected cells susceptible to antivirals ang immune recognition.
See this image and copyright information in PMC

References

    1. zur Hausen H, de Villiers EM. Cancer “causation” by infections–individual contributions and synergistic networks. Semin Oncol (2014) 41:860–75. doi: 10.1053/j.seminoncol.2014.10.003 - DOI - PubMed
    1. Varn FS, Schaafsma E, Wang Y, Cheng C. Genomic characterization of six virus-associated cancers identifies changes in the tumor immune microenvironment and altered genetic programs. Cancer Res (2018) 78:6413–23. doi: 10.1158/0008-5472.CAN-18-1342 - DOI - PMC - PubMed
    1. Kitsou K, Iliopoulou M, Spoulou V, Lagiou P, Magiorkinis G. Viral causality of human cancer and potential roles of human endogenous retroviruses in the multi-omics era: An evolutionary epidemiology review. Front Oncol (2021) 11:687631. doi: 10.3389/fonc.2021.687631 - DOI - PMC - PubMed
    1. Longnecker R, Neipel F. Introduction to the human gamma-herpesviruses. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K, editors. Human herpesviruses: Biology, therapy, and immunoprophylaxis. Cambridge: Cambridge University Press; (2007). - PubMed
    1. Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from burkitt’s lymphoma. Lancet (1964) 1:702–3. doi: 10.1016/S0140-6736(64)91524-7 - DOI - PubMed

Publication types