Viruses: the ally or the enemy?

Introduction

Viruses are often considered monsters; they cause disease, ruin crops, and sometimes cannot be treated by medical means. However, in recent years, science has allowed us to harness the therapeutic potential of viruses. Through the research of many virologists and engineers, viruses now have the potential to cure or treat disease; however, does this outweigh the fact that viruses have killed millions in the past? Can viruses be the ally, or will they always remain the enemy?

What is a virus?

A virus is a small obligate parasite that requires host cells from another organism in order to replicate [3]. There are many different types of viruses; they are categorized based on their genetic material and the proteins they express [18]. Viruses have tropism towards cells of specific organisms depending on their viral structure. Every virus has to bind to a specific viral receptor, which is a surface protein on the host cell that facilitates attachment and entry into host cells [19]. If the viral receptor does not match the secondary receptors, the virus’s surface proteins, the cell will not let the virus in and thus the virus will not be able to infect the cell, replicate itself, and eventually burst out of the cell to infect more [19].

The enemy

Viruses can cause disease in the organisms they infect. In humans, they have been known to cause smallpox, herpes, poliomyelitis, ebola hemorrhagic fever, aids, rabies and even the common cold [15].

Although viruses are not considered to be living, they do contain genetic material. The genetic material in viruses is susceptible to mutation due to the error-prone polymerases that replicate their genomes, which can lead to many variations of the same type of pathogenic virus [24]. Genetic variation in the same type of virus can be detrimental when combating disease, as vaccines and antivirals are usually made for specific strains of virus [24]. As a result, the variations of viruses that bypass treatment can continue to thrive through natural selection and they are more likely to be drug resistant than the original [24]. An example of this can be seen with the influenza virus; in order to combat the virus and prevent serious illness, an influenza vaccine, or flu shot, can be taken. The flu shot is an inactive version of the influenza virus that is predicted to circulate during the flu season of any given year, it works by producing a protective immune response against the influenza virus [24]. However, the flu shot does not encompass all variations of the virus and so people may still end up with the flu. This example demonstrates how variations in pathogenic viruses can be difficult to treat.

Variation in pathogenic viruses is an important issue as it may give rise to new pathogenic diseases. For example, in Cameroon, West Africa, scientists have found dead animals with traces of new pathogenic viruses similar to pathogenic viruses observed in the past, such as HIV [9]. This shows that a virus has the potential to mutating into a new, more potent variation of the virus. Researchers predict that if new pathogenic viruses could arise by mutation in animals, the same could occur in humans as well, especially when developing countries lack proper sanitation infrastructure and access to healthcare [9]. This can potentially lead to new virus and disease outbreaks [5].

The ally

Through the past 20 years of research, scientist and engineers have found ways to alter virus function for gene therapy, combating antibiotic and pesticide resistance, addiction therapy and cancer treatments. Each method will be discussed briefly to understand the mechanisms, future applications, comparisons to present treatment options, and limitations.

Gene therapy

Gene therapy and modification refers to the use of genetically modified viruses to deliver, exchange or inactivate a gene to treat genetic disease [1]. This is accomplished by taking a healthy copy of the gene and inserting it into the virus genome through plasmodials or nanostructures [6]. The virus is then delivered to the infected individual via either the in vivo or ex vivo method [16]. In vivo delivery involves delivering the modified viral DNA directly into organ tissue, which causes production of a therapeutic protein in the target tissue [16]. Ex vivo involves infecting a surrogate cell culture with the viral genome, resulting in expression of therapeutic proteins in these cells, which are then transplanted into the organ system.16 Some limitations that restrict the development and research of gene therapy include the risk of inducing disease by injecting the organ tissue, difficulty releasing the gene in stem cells, rejection of the viral genome, and the ethics behind the research [20]. Gene therapy, when further developed, is promising for the treatment of recessive genetic disorders such as cystic fibrosis, hemophilia, muscular dystrophy, sickle cell anemia and complex diseases such as Alzheimer’s [6]. Previous clinical trials and research targeting these diseases have produced mixed results. Gene therapy should be further researched as viral vectors are an effective way of replacing dysfunctional genes with normal genes.

Combating antibiotic and pesticide resistance

Antibiotic and pesticide resistance is a growing problem in North America due to the excessive use of antibiotics [21]. As a consequence of the abuse of antibiotics, superbugs—antibiotic resistant bacteria—are becoming more prevalent, causing people to die from previously treatable diseases [21]. It is predicted that by the year 2050, if no action is taken to combat antibiotic resistance bacteria, the number of people who die from associated diseases will outweigh cancer deaths, with more than 10 million cases per year [21]. Fortunately, researchers are currently altering specific viruses known as bacteriophages or phages, to infect antibiotic resistant bacteria [13]. Phages can bypass the bacterial immune system in order to infect and replicate within the bacteria. Usually, bacteria have an immune response mechanism known as CRISPR that protects themselves from phages by degrading down phage DNA and recording it for future recognition [17]. The altered phages that are currently being developed are designed to hijack CRISPR, allowing them to degrade the bacteria’s antibiotic resistant genes [13]. Some limitations to this research include the unknown side-effects of having a large number of altered phages in one’s body. According to the American National Library of Medicine, a clinical trial tested the use of the bacteriophages to combat Pseudomonas aeruginosa, an antibiotic-resistant bacteria found in the intestines [10]. A dosage of phages was administered alongside antibiotics, producing very successful results.10 In addition, bacteriophages can be used to kill pesticide resistant insects without harming the plant itself [13]. These methods have so far shown very promising results and will make a huge impact in the future especially since antibiotic and pesticide resistance are growing problems.

Addiction treatments

Addictions typically begin with the release of dopamine in the reward system of the brain [8]. Drugs such as cocaine not only release large amounts of dopamine but also block the reuptake of dopamine in the neuronal synapses via the dopamine transporters [8]. Through viral therapy, however, protein-based therapeutics could be designed to bind and sequester the cocaine. This would degrade the molecules and reduce its psychoactive effects [8]. Limitations to this method of addiction treatment include limited funding and long-term implications. Although, this treatment has proven effective in rodent models, it has yet to be tested in clinical trials [8].

Cancer treatments- oncolytic virus therapy

In recent years, scientist have been able to create “oncolytic viruses” that can have one of two main functions: to find, infect, and kill tumor cells without harming healthy cells or to alert the immune system of the presence of cancer [11]. Thus far, The Food and Drug Administration (FDA) has officially approved one oncolytic virus [14]. This virus is a genetically modified form of the herpes virus and has been successful in treating melanoma, a type of skin cancer [4]. The oncolytic virus does this by seeking out a specific marker protein called αvβ6 integrin which is a marker protein which is only found in skin cancers [4]. Once it finds this marker, the virus is then able to invade the cell, reproduce, and cause lysis of the cell, allowing the immune system to detect and target the rest of the tumor [7]. The viral DNA could also trigger the host cell to produce antibodies which in turn help the immune system if there is a recurrence of the cancer in the future [7]. Currently cancer treatments such as chemotherapy, radiation and surgery have negative side effects that are not present in oncolytic virus therapy.

There are many forms of viruses currently being developed in hopes of treating other types of cancer, and clinical studies are still underway. At McMaster University and the University of Ottawa, specific studies are currently underway for engineering viruses from Brazilian sandflies to create a therapy called MG1-MAGEA3 which has the potential to treat lung, breast, and esophageal cancers [11]. Dr. Mossman, a pathology and molecular medicine professor and researcher at McMaster, also developed a form of oncolytic viral therapy that is currently making a breakthrough in the world of medicine [23].

Conclusion

Viruses, despite being seemingly simple creatures, have the ability to affect the world either positively or negatively.  In the past, millions of people have died due to viral disease. In the future, however, they have the potential to create new and improved methods of gene therapy, combating antibiotic and pesticide resistance, addiction treatments and cancer treatments. Further research must be conducted to truly determine out whether they are the ally or the enemy.

Written by Linah Hegazi

Mentored by Jessica Chee

 

References:
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