HABIBA ABBASI
We have heard an awful lot about viruses since the Coronavirus pandemic has swept the nation, creating uncertainty and shaking families by the unexpected loss of loved ones. But, what are viruses? And more importantly, what do they want?
Let us start at the beginning. A virus is a very small organism that requires the cells of other organisms to survive and reproduce. They are composed of DNA or RNA (the material that carries all the information about how a living thing will develop and function), a protein coat and sometimes an envelope.
Structure of a virus (SOURCE: https://www.sciencelearn.org.nz/resources/184-virus-strains)
Although these ubiquitous organisms have been roaming the planet for time immemorial, they were actually first discovered in the nineteenth century by Ivanovski and Beijerinck during their study of the Tobacco mosaic virus. In 1892 Ivanovski established that extracts from infected tobacco leaves were still infectious after filtration to remove bacteria. Subsequently, in 1898 Beijerinck discovered that this infectious substance was able to replicate and multiply in living plants.
It is important to note that not all viruses cause disease in humans. It turns out that they are quite selective about the cells that they infect! Even though their names are derived from the Latin word for “poison”, not only are they needed to support much of the life on Earth but they have also proven to be useful in several healthcare contexts including (but not limited to) antibiotic resistance, fighting infectious disease and cancer therapeutics.
PHAGE THERAPY
The WHO has stated that antibiotic resistance is one of the biggest threats to global health today. Antibiotic resistance occurs when bacteria develop the ability to survive the antibiotics that are designed to kill them, arising as a result of overuse and misuse of antibiotics.
Bacteriophages are viruses that selectively target and kill bacteria can be used as a potential solution to this problem. These viruses enter bacterial cells and use their replication machinery to produce more viruses and kill the bacterial cell in the process.
A paper published in Antibiotics explains that the advantage of using bacteriophages as opposed to antibiotics is that they are much more specific in the bacteria that they target. This lack of specificity in antibiotics means that they can also kill useful bacteria during their treatment and contribute to the spread of antibiotic resistance.
In an interview with Dr. Antonia Sagona, Associate Professor of Infection and Microbiology at the University of Warwick, she explains that “phage therapy is already used in many countries in the world, including Israel, Russia, Finland and USA”.
Although there are limitations of the use of bacteriophages in humans including the potential immune response triggered by their use, Dr. Sagona assures that “to avoid immune response, phages are carefully purified with advanced purification methods and are tested for endotoxins. Purified phages with very low endotoxin levels do not create an immune response and are safe to be used for patients”.
Dr. Sagona explains that the next steps for phage therapy include “more research to ensure long term safety and interactions with antibiotics and other antibacterial agents”. Moreover, “interaction between phages, bacteria and human cells or specific conditions in the human body” are required to ensure the safe application of phage therapy in humans.
Correspondingly, phage therapy was used in the UK for the first time in 2019 to treat a fifteen year old patient with a lung infection due to complications with cystic fibrosis. Following the failure of antibiotics to treat the infection, phage therapy was used to effectively treat the patient.
Dr. Graham Hatfull, who led the development of this phage therapy at the University of Pittsburgh explained “we didn’t think we’d ever get to a point of using these phages therapeutically. It’s a brilliant outcome”. As a result, we can be optimistic about the potential use of bacteriophages in the clinical treatment of bacterial infections.
ONCOLYTIC VIRUSES
If phage therapy was not a convincing enough use of viruses, another remarkable use of viruses is in the destruction of cancerous cells. Namely, these viruses are called oncolytic viruses. Traditional methods of cancer therapy include surgery, radiotherapy and chemotherapy, but some of these treatments are ineffective and costly. Oncolytic viruses can selectively reproduce in cancer cells and kill them whilst sparing healthy cells.
An example of such use is oncolytic adenovirus in the treatment of advanced breast cancer. Early stages of breast cancer can be treated easily, however, the currently available treatment techniques are less effective in advanced stages of the disease.
A study conducted at the Beijing University of Technology confirmed the use of oncolytic viruses in the treatment of breast cancer cells. The authors conclude by explaining that this therapy is “rapidly emerging as a promising weapon in the fight against cancer” and “clinical trials are warranted to confirm the possible use of this innovative treatment approach in clinics and move it from bench to bedside”.
VIRAL COINFECTION
Another surprising benefit of viruses is infection with certain viruses can fend off some pathogens in humans. For instance, infection with the human pegivirus (GBV-C) has been shown to improve survival in Ebola infected and HIV positive individuals by altering immune cell activation.
A study conducted by researchers at the University of Iowa discovered that “GBV-C infection leads to diminished immune activation and T cell proliferation that limits HIV replication and slows disease progression”.
Although this virus has proven to be protective against certain diseases, the authors propose that “future studies are needed to further understand the mechanisms by which GBV-C alters immune activation and T cell proliferation pathways”. Inevitably the ultimate question arises – are there more viruses yet to be discovered that can defend against other infectious diseases in humans?
Everything considered, even though these conniving organisms have wrought havoc and will continue to do so, it seems viruses have a greater purpose and have proven to be beneficial to humanity. Thus, it is important to maintain a balanced view of viruses and accept that they are not our arch-enemy, instead, like us, they are organisms trying to survive on this planet that we all inhabit.
REFERENCES
Antibiotics Resistance. (2020). World Health Organisation. https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance.
Bhattarai, N., & Stapleton, J. (2012). GB Virus C: the good boy virus? Trends in Microbiology, 23(1), 1–7. https://doi.org/10.1016/j.tim.2012.01.004.
Cao, G. D., He, X. B., Sun, Q., Chen, S., Wan, K., Xu, X., Feng, X., Li, P. P., Chen, B., & Xiong, M. M. (2020). The Oncolytic Virus in Cancer Diagnosis and Treatment. Frontiers in Oncology, 10(September), 1–12. https://doi.org/10.3389/fonc.2020.01786.
Derek, L., Koskella B, Henry, L., Vazquez-Sandoval A, Ghamande S, Surani S, Strohl M, Zhang X, & Bessissow, L. D. (2017). Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. 8(3), 3. http://www.f6publishing.com.
First use of pioneering phage virus therapy to treat patient with cystic fibrosis. (2019). https://www.gosh.nhs.uk/news/first-use-pioneering-phage-virus-therapy-treat-patient-cystic-fibrosis/.
Romero-Calle, D., Benevides, R., Geos-Neto, A., & Billington, C. (2019). Bacteriophages as alternatives to antibiotics in clinical care. Antibiotics, 1–5.
Lauck, M., Bailey, A. L., Andersen, K. G., Goldberg, T. L., Sabeti, P. C., & O’Connor, D. H. (2015). GB Virus C Coinfections in West African Ebola Patients. Journal of Virology, 89(4), 2425–2429. https://doi.org/10.1128/jvi.02752-14.
Sakhawat, A., Ma, L., Muhammad, T., Khan, A. A., Chen, X., & Huang, Y. (2019). A tumor targeting oncolytic adenovirus can improve therapeutic outcomes in chemotherapy resistant metastatic human breast carcinoma. Scientific Reports, 9(1), 1–11. https://doi.org/10.1038/s41598-019-43668-8.