Viruses are microscopic infectious agents. Their size ranges from 20 to 400 nanometers. In another words, they are 500 times smaller than a red blood cell, or 500 000 times smaller than a housefly. Indeed, they are very simple agents, composed of genetic material (DNA or RNA) surrounded by a shell made of protein. They can infect a wide range of living organisms, from bacteria to humans. In complex organisms like humans, viruses recognize and infect specific cells. For example, the Hepatitis B Virus specifically infects hepatocytes, also known as liver cells. When a virus infects a host cell, it hijacks the normal cellular machinery to produce new virus particles. There are a variety of viruses leading to various diseases. For example, HIV is responsible for causing acquired immunodeficiency syndrome (AIDS), SARS-CoV-2 is responsible for COVID-19, and influenza viruses are responsible for the flu. Furthermore, certain viruses, known as oncogenic viruses, can contribute and induce tumour development, while others, called oncolytic viruses, can potentially kill cancerous cells, and activate your immune system to destroy these cancer cell as well. This blog post explores the bad side of oncogenic viruses and the good side of oncolytic viruses.
Oncogenic Viruses: A Well-Known adversary
Oncogenic viruses are those capable of causing cancer. There are seven known oncogenic viruses:
- human papillomaviruses (HPV),
- Epstein-Barr virus,
- hepatitis B virus,
- hepatitis C virus,
- human T-cell lymphotropic virus,
- Kaposi's sarcoma-associated herpesvirus,
- Merkel cell polyomavirus.
It’s estimated that these viruses are responsible for approximately 10% of cancer cases worldwide [1]. HPV, for instance, is strongly associated with cervical cancer, as well as malignancies in other regions such as anal, vaginal, penile, and oropharyngeal cancers [2]. Interestingly, studies have shown that some viruses like HIV are not oncogenic by themselves but could promote cancer development in combination with an infectious agent [3] .
Oncogenic viruses employ various mechanisms to promote cancer development. They can produce proteins which interfere with cell functions. For example, HPV expresses viral proteins E6 and E7. These proteins inhibit different cellular proteins from the host which have a role in the control of cell proliferation. Thus, the viral proteins E6 and E7 make host cells proliferate in an uncontrolled manner, allowing for the initiation of cancer. [4].
Moreover, viruses play a role in modifying the normal and “healthy” tissue surrounding the tumour. Indeed, they induce chronic inflammation, generating molecules which contribute to DNA damage, leading to mutations. These mutations can affect important genes for cell control and thus participate in tumour initiation. Additionally, when viruses infect cells, the immune system is activated to mount a defence against this infection. However, some viruses have evolved mechanisms to evade immune defence, allowing them to stay within the body. These persistent infections can lead to a decrease of immune system activity and an increased risk of cancer development [5]. Thus, viruses can be responsible for cancer initiation and progression by taking control of cellular machinery and modifying the microenvironment.
Oncolytic Viruses: A New Ally in Cancer Therapy
In contrast to oncogenic viruses, oncolytic viruses are gaining interest as potential therapeutic agents for cancer treatment. Oncolytic viruses, natural or created artificially, preferentially infect, and destroy cancer cells while sparing healthy cells [6]. Their name comes from Onco, for cancer, and Lytic, for lysis. Therefore, these are viruses that lyse cancer cells.
These viruses can be directly injected into tumours or administered intravenously. To work, they first enter a tumour cell. Once inside, they replicate to create new viruses. When the virus quantity within the cell reaches a maximum number, the cancerous cell bursts and dies. To further induce the death of cancer cells, they can also stimulate the immune system, which in turn will target cancerous cells, leading to their destruction [7, 8]. Furthermore, oncolytic viruses can be modified and improved to safely deliver therapeutic genes directly into cancer cells, enhancing the effectiveness of treatments. For example, talimogene laherparepvec (T-VEC), an oncolytic virus, has been rendered more safe by deleting genes responsible for disease associated with the natural unmodified virus. Moreover, this modified virus has a gene which improves the recruitment of immune cells against the tumour. [6].
Promising results have been observed in clinical trials using oncolytic viruses across various cancer types, including melanoma, glioblastoma, and advanced or metastatic cancers. T-VEC, for instance, has been approved for the treatment of advanced melanoma in the USA, Europe, and Australia, with an ongoing clinical trial for Canadian approval [6].
The development of oncolytic viruses represents a novel approach to cancer therapy, combining virology, immunology, and gene therapy. While challenges remain, such as optimizing viral delivery, enhancing tumour selectivity, and overcoming immune responses against the virus, oncolytic viruses hold great potential for improving cancer treatment outcomes and complementing existing therapies.
Conclusion
As we seen here, some viruses could be involved in cancer development and some other be a new weapon against cancer. This knowledge opens avenues for cancer research, prevention, and therapy. For instance, vaccination against HPV has been shown to reduce the risk of developing high-grade histologically proven cervical abnormalities by 85% [9]. Exploring and expanding our understanding of viruses can help us discover additional oncogenic or oncolytic viruses, leading to prevention strategies such as vaccination and innovative approaches like anti-viral or oncolytic virus therapies.
References :
1. Plummer, M., et al., Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health, 2016. 4(9): p. e609-16.
2. Schiller, J.T. and D.R. Lowy, An Introduction to Virus Infections and Human Cancer. Recent Results Cancer Res, 2021. 217: p. 1-11.
3. Lucas, S. and A.M. Nelson, HIV and the spectrum of human disease. J Pathol, 2015. 235(2): p. 229-41.
4. Chen, J., Signaling pathways in HPV-associated cancers and therapeutic implications. Rev Med Virol, 2015. 25 Suppl 1: p. 24-53.
5. White, M.C., X. Wu, and B. Damania, Oncogenic viruses, cancer biology, and innate immunity. Curr Opin Immunol, 2022. 78: p. 102253.
6. Shalhout, S.Z., et al., Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol, 2023. 20(3): p. 160-177.
7. Roy, D.G., et al., Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination. Nat Commun, 2021. 12(1): p. 2626.
8. Tian, Y., D. Xie, and L. Yang, Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduct Target Ther, 2022. 7(1): p. 117.
9. Garland, S.M., et al., Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience. Clin Infect Dis, 2016. 63(4): p. 519-27.