InterClinical Practitioner eNews March 2020 Issue 103
What is a virus?
Viruses vary widely in shape and complexity. They do not contain the chemical machinery needed to carry out chemical reactions for life. Instead a virus carries only nucleic acid, with a set of genetic instructions, and a coat of protein to protect it. Enveloped viruses have an extra surrounding covering made of a lipid membrane. A virus must have a host cell in which to live and replicate. Outside this host, a virus cannot function.
Viruses have a remarkable ability to adapt to new hosts and environments. This mutation happens faster in RNA viruses than DNA viruses; single-stranded viruses mutate faster than double strand viruses and these mutations can be passed to the next generation. In viruses, a generation is often defined as a cell infection cycle.1 This high rate of mutation is thought to confer a survival advantage to viruses, allowing a rapid response to environmental change.2 Novel mutant strains continuously emerge causing influenza pandemic outbreaks.3
The host and its effect on a virus
Nutritional deficiency, causing increased oxidative stress, may lead to a rise in free radicals that could damage the RNA sequence of a virus, resulting in mutations.2 This can cause the rapid selection of a new viral consensus sequence that may be due to a decrease in the host’s immune function. This decrease in immune function can be accompanied by an increase in viral load, which allows for a more virulent genotype to outcompete the original consensus sequence and result in a new sequence.
The host’s nutritional factors can have a profound effect on a viral pathogen and can result in the expression of a new and more virulent pathogenic phenotype.2 Immune dysfunction in the host does not only lead to susceptibility to viral infection, but can directly affect the virus itself. It will then be free to affect not only nutritionally deficient populations but well-nourished populations as well.
This was seen in the study of coxsackievirus A9 meningitis in Cuba. When the virus was replicated under conditions of oxidative stress, it leads to the emergence of a new strain with altered pathogenesis.2
This has important implications for the role of nutrition and infection. It suggests that the host’s nutritional status is about more than individual wellbeing. Poor nutritional status can alter the genome of a virus and affect others.2
What nutrients support the immune system to fight viral infection? Nutritional status is closely associated with the severity and susceptibility to infectious disease. Inadequate nutrition impairs the functioning of the immune system and results in increased susceptibility to infection.4
The association between famine, epidemics of infectious disease, and high rates of mortality have been noted throughout history. It is postulated that nutritional deficiencies cause changes in immune system function thereby opening the door to infection. Animal studies examining the effect of malnutrition and protein deficiency on the susceptibility to infection, have found greater viral severity that persists longer with a higher viral load.4
It is well known that zinc deficiency results in a compromised immune system. Topical zinc application studies have been performed in humans which demonstrated a significantly reduced recurrence and duration of infection from herpes simplex virus.5 Most clinical studies using zinc supplementation are primarily limited to rhinovirus infection and have demonstrated decreased clinical symptoms in volunteers after being given zinc.4 These studies are dependent on the amount of ionic zinc present at the sight of infection (oral and nasal mucosa) and where high doses of ionic zinc were used, there was a clear reduction in cold duration.5
Metallothioneins, small cysteine rich proteins that store and transfer zinc, are also involved in immune responses. Oxidative stress induces zinc release from metallothioneins to reduce reactive oxygen species generated by viral infection. When stimulated by interferons, metallothioneins induce the expression of hundreds of antiviral genes. Interferons possess diverse roles that include immune cell activation and direct antiviral activity.
Although zinc possesses direct antiviral properties it is also critical in generating both innate and acquired (humoral) antiviral responses. Zinc is an integral part of many viral enzymes which highlights the importance of regulating cellular and systemic zinc distribution to inhibit viral replication and dissemination.5
In an animal study a deficiency in selenium has been found to increase susceptibility due to immune suppression. A deficiency in this mineral allowed for a pre-existing virus to mutate. This may be due to the fact that selenium is an essential co-factor for glutathione peroxidase, an enzyme important in limiting oxidative stress in the host. This paves the way for an impairment of the immune system which in turn leads to an increase in viral load and the possibility of generating mutations in the virus with greater pathogenic potential.4
Vitamin E acts as a free radical scavenger and works in tandem with selenium, sparing one another’s activities. An individual with a deficiency in vitamin E will lean toward a pro-oxidative state. As with selenium, a deficiency of this vitamin will increase oxidative stress and cause an increase in viral pathology.4
Vitamin C is one of the best known immune supporting nutrients but its effects are controversial. What is known with certainty, is that an insufficiency of vitamin C severely impacts multiple organs and resulting in impaired immunity and a higher susceptibility to infections. It cannot be synthesized by humans due to the loss of a key enzyme in the biosynthetic pathway.6
A study conducted on mice (Gulo knockout mice) without the ability to synthesise vitamin C, concluded that vitamin C shows an antiviral immune response in the initial stages of influenza infection. Supplementation of vitamin C after infection did not have any effect. The study concluded that ‘it might be possible by maintaining sufficient levels of vitamin C to effectively prevent in vivo pathogenesis of influenza at the initial stage of viral infection'.7
Vitamin A is perhaps the best studied nutrient with regard to viral infection. More is known about how it modulates immune function than for any other micronutrient. Much attention has been focused on the relationship between vitamin A deficiency and infection with the measles virus. Investigation led to the discovery that a deficiency in vitamin A often accompanied the development of severe measles. Treatment with vitamin A increased the levels of measles-specific IgG and increased the total numbers of lymphocytes in infected children.4
The severity of other viral infections, such as RSV (respiratory syncytial virus), rotavirus and herpes simplex, increased in the presence of a deficiency of vitamin A.4 Vitamin A deficiency causes pathological changes in the epithelium of the respiratory tract, including keratinization and loss of ciliated cells, mucus and goblet cells.8
Studies conducted in Papua New Guinea on children infected with malaria showed a significant reduction in the incidence of attacks after supplementation with Vitamin A. Individuals with poor nutritional status and vitamin A deficiency are shown to be at major risk for the progression of tuberculosis.8 Herbal immune support Licorice Licorice (Glycyrrhiza glabra) is a common herb which has been used in traditional Chinese medicine for centuries.
Recent studies have shown that it possesses many properties, one of which is the ability to support the immune system to combat viral infections. The main active components are glycyrrhizin (GL) and 18β-glycyrrhetinic acid (GA). Many studies have shown GL to be an effective antiviral compound to numerous viruses by weakening viral activity, inhibiting virus gene expression and replication, reducing adhesion force and stress, and reducing HMGB1 (which has a potentially pathogenic role in viral diseases) binding to DNA. Compared with GL, the studies on the antiviral activity of GA are limited. However, the antiviral mechanisms of these compounds are similar. GA exerts its antiviral activity also by inhibiting virus replication, preventing viral attachment or enhancing host cell activity.9
Panax (Korean) Ginseng
Korean ginseng contains various pharmacologically active substances, the most bioactive being ginsenosides. Extracts of Korean ginseng have been tested against a whole array of viral infections including influenza, rhinovirus, herpes, hepatitis, rotavirus and many more. Its foremost effect has been the enhancement of host immunity, but it can also exert direct antiviral effects by inhibiting viral attachment, membrane penetration and replication.3
Throughout history many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. When garlic is chopped or crushed, allinase enzyme is activated and produces allicin. It is allicin that is the principal bioactive compound present in garlic.10
Although very little work has been done to investigate its antiviral properties, a few studies have reported that garlic extract showed in vitro activity against many common viral infections.11
Although extremely small in size and simple in structure, viruses cause numerous diseases. They are exceedingly adaptable and able to mutate to suit their environment. This viral adaptation is passed on to the next generation. The severity of infection is greatly affected by the host’s nutritional status. By being conscious of our nutritional intake we can help to improve our immune system and support its ability to repel and recover from viral infections.
1. Sanjuán, R., & Domingo-Calap, P. (2016). Mechanisms of viral mutation. Cellular and Molecular Life Sciences, 73(23), 4433–4448. doi:10.1007/s00018-016-2299-6
2. Beck, M. A., & Levander, O. A. (2000). Host Nutritional Status and Its Effect on a Viral Pathogen. The Journal of Infectious Diseases, 182(s1), S93–S96. doi:10.1086/315918
3. Im, K., Kim, J., & Min, H. (2016). Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection. Journal of Ginseng Research, 40(4), 309–314. doi:10.1016/j.jgr.2015.09.002
4. Beck, M. A. (1996). The role of nutrition in viral disease. The Journal of Nutritional Biochemistry, 7(12), 683–690. doi:10.1016/s0955-2863(96)00132-5
5. Read, S. A., Obeid, S., Ahlenstiel, C., & Ahlenstiel, G. (2019). The Role of Zinc in Antiviral Immunity. Advances in Nutrition. doi:10.1093/advances/nmz013
6. Carr, A., & Maggini, S. (2017). Vitamin C and Immune Function. Nutrients, 9(11), 1211. doi:10.3390/nu9111211
7. Kim, Y., Kim, H., Bae, S., Choi, J., Lim, S. Y., Lee, N., … Lee, W. J. (2013). Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection. Immune Network, 13(2), 70. doi:10.4110/in.2013.13.2.70
8. Semba, R. D. (1999). Vitamin A and immunity to viral, bacterial and protozoan infections. Proceedings of the Nutrition Society, 58(03), 719–727. doi:10.1017/s0029665199000944
9. Wang, L., Yang, R., Yuan, B., Liu, Y., & Liu, C. (2015). The antiviral and antimicrobial activities of licorice, a widelyused Chinese herb. Acta Pharmaceutica Sinica B, 5(4), 310–315. doi:
10.1016/j.apsb.2015.05.005 10. Weber, N., Andersen, D., North, J., Murray, B., Lawson, L., & Hughes, B. (1992). In VitroVirucidal Effects ofAllium sativum(Garlic) Extract and Compounds. Planta Medica, 58(05), 417–423. doi:10.1055/s-2006-961504
11. Bayan, L., Koulivand, P. H., Gorji, A. (2013). Garlic: a review of potential therapeutic effects. Avicenna Journal of Phytomedicine, 4(1): 1-14.