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  • Doctor’s Health Advice
  • Yuzo Endo, M.D., Ph.D.
  • Masahito Hitosugi, M.D., Ph.D.
  • John E. Lewis, Ph.D.

Doctor’s Health Advice

Doctor’s Health Advice

Infectious Diseases and Immunity

No. 4

Treatment and Prevention of Viral Infections: Antiviral Drugs, Serum Therapy, and Immunity

It was just before the 20th century that the existence of viruses was discovered. Unglazed pottery played an important role in the conceptual discovery of viruses. They had small pores on their surface, which were thought to be too small for most species of bacteria to pass through. At the same time, however, researchers anticipated the existence of creatures that were small enough to pass through the pores. They were called “filterable microorganisms,” and were widely studied by many researchers, including the famous Louis Pasteur. Hideyo Noguchi, who passed away while researching microorganisms for yellow fever, was also among them,

Tobacco mosaic disease seriously damages tobacco cultivation. Beijerinck, a Dutch microbiologist and botanist, proved the existence of filtrate tobacco mosaic microorganisms in 1898. He was the first researcher to use the word “virus” in a published study. Subsequently, Stanley succeeded in crystallizing tobacco mosaic virus. This finding was followed by discoveries of Rickettsia, whose size is between viruses and bacteria, and bacteriophages. These findings paved the way for the era of gene research. At the present time, a chemical substance called a “collodion membrane” is used instead of unglazed pottery in virology research.

Several viruses cause serious health risks to human beings. Representative examples are smallpox virus, yellow fever virus, rabies virus, and poliovirus. Research on virology and vaccine development progressed in order to overcome these infections. With hepatitis, several species of hepatitis viruses were discovered; hepatitis A virus, which is a type of epidemic hepatitis, and hepatitis B and C viruses, which are both post-transfusion types of hepatitis (serum hepatitis). The HIV virus also attracted a lot of attention. This virus was originally considered to be a monkey virus and was called SIV (Simian Immunonodeficency Virus). It mutated, however, to become infectious to humans, and was later named HIV (Human Immunodeficiency Virus). HIV aroused worldwide alarm. Virus infections have their own species specificities, and mutated smallpox viruses include human, simian, swine, and bovine species. There has been speculation on what species was used for smallpox vaccination.

Smallpox vaccination is generally supposed to have been developed from bovine smallpox virus. It means that the smallpox vaccine can protect human beings by preventing infection or reducing symptoms, even if it is derived from a mutated smallpox virus of an animal species. A vaccination that provides “complete antibody” production can prevent smallpox infection. “Complete antibody” refers to an antibody that attaches to a virus antigen and is subsequently cleared from the body by macrophage phagocytosis. This activity of antibodies is enhanced by the complement system, which is a part of the immune system. This sequence of activities is called opsonization, which is the mechanism by which antigenic substances are connected to antibodies and complement proteins (immune complement) and removed. In other cases, antibodies that don’t possess opsonization activity are called “incomplete antibodies.” Based on these facts, it is unpredictable which antibody will be produced, complete or incomplete, and the accidental nature of this can’t be eliminated in the vaccine development process. It is a very demanding challenge to develop a new vaccine.

It may not be too much to say that the ultimate goal of virus research is vaccine development. For the first step, a virus needs to be cultured by pure cultivation. Goodpasture was the first researcher who used eggs in pure cultivation of viruses. This method brought a revolutionary advancement to vaccine production processes. At the same time, a method of almost perpetually maintaining cultured cells was successfully developed. The research for developing vaccines is indispensable in preventing infections or alleviating symptoms. In the vaccine development process, viruses are mass-cultured without using human bodies, and non-infective antigens derived from non-infective viruses are administered to induce production of highly specific, complete antibodies (mainly consisting of IgM and IgG, and to some extent, IgA). This kind of virus has been desired by human beings on earth, and is like a long‐awaited, blessed rain after a long spell of dry weather.

During that time, scientists learned, from the accumulated findings of pathological anatomy, that viruses have their own organ-specificities. It was also learned that viruses could be roughly categorized into acute and chronic viruses. Acute viral infections are highly cytotoxic, and infected patients either recover or die. For example, although measles was thought to be a mild disease, it sometimes causes encephalitis. Severe measles patients are treated with serum therapy, in which purified blood serum of recovered human patients, or a perfect antibody from a preparation of a gamma globulin formulation is administered. Serum therapy was first developed as an antitoxin therapy for diphtheria, and was named after its developers, Bering and Shibasaburo Kitasato. Its principle is still clinically applied.

Unlike acute viral infections, chronic ones are parasitic inside human cells. These viruses exist as endogenous viruses and destroy host cells to proliferate when the host has health challenges. These species of virus include chickenpox virus and herpes virus. Moreover, some viruses may be regarded as tumor viruses rather than infectious disease. This type of virus includes human papillomavirus, which induces cervical carcinoma, Epstein-Barr virus, which induces malignant lymphoma, human leukemia/lymphoma viruses, and hepatitis virus. These viruses have been considered to be involved in tumor development after an extended latent period. Viruses are attacked by infiltrating macrophages and neutrophils with the release of active oxygen in areas of virus infections or microinflammations, which can occur in any organ. This activity, however, gradually damages DNA in the cells and can lead to cancer development after a latent period greater than ten years.

The difference between acute and chronic viral infections depends on the balance between the innate and acquired immune systems. Some studies show that the antigen recognition and antibody production ability of immune cells may be at their peak at around 35 years of age. One of the most important organs in the human body that declines with age is the bone marrow. As mentioned above, viral infections that develop in early childhood are often in a latent condition in cells. These viruses hiding in cells are inaccessible to the immune system. When the immune balance in an adult body is damaged by excessive stress and a poor health condition, viruses, such as herpes virus enclosed in nerve cells, are activated and cause small blisters developed alongside the nerve. Herpes labialis (oral herpes) is common in students just before exams. The frequency of recurrence of these diseases increases with age.

Finally, let me mention the most frightening aspect of infectious disease. When a viral infection increases in severity, the human self-defense system sometimes overreacts. This phenomenon is expressed in the term “cytokine storm,” or “multiple organ dysfunction.” Various immune cells respond to invaders by secreting cytokines (chemical messengers). In normal conditions, cytokines are secreted by immune cells in the blood and peripheral tissues under careful regulation. When the invader is too strong, however, the immune cells lose control and secrete cytokines excessively or in an unbalanced manner. This phenomenon is called a cytokine storm. Dexamethasone, an immunosuppressive agent, was selected as a treatment agent for COVID-19 infection. This fact indicates that it is a very troublesome infection. Severe symptoms are more likely to occur, especially in the elderly with advanced bone marrow atrophy, and in people with underlying diseases. Whatever the case may be, based on the idea of “shokui dōgen” (food-medicine-same root), which is a traditional Japanese idiom that means that medicine and food share the same foundation, we need to strengthen our physical health by having a healthy diet and appropriate dietary supplements.

 

Source Literature:

Virus Hunters by Greer Williams 1959; C. E. Tuttle Co., Tokyo

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Yuzo Endo, M.D., Ph.D.

Yuzo Endo, M.D., Ph.D.
Hamamatsu University School of Medicine

1969.9: Graduated from Medical School, University of Tokyo Consultant pathologist in Hamamatsu University, Medical School, and Fujimoto General Hospital. Medical Consultant in conventional and integrative medicine.

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