By Kelly A. Reynolds, MSPH, PhD
Avirus commonly isolated from water is in the news again. This time, the mimivirus has been linked to patients with rheumatoid arthritis. Researchers hypothesize that these water-based, naturally occurring viruses trigger auto-immunity to collagens, which can result in joint inflammation. This research supports the long-held belief by many that viruses in the environment may be responsible for a host of auto-immune disorders.
Mimiviruses: a new pathogen?
Relative to the microbial world, mimiviruses (i.e., Acanthamoeba polyphaga mimivirus) are extremely large, approaching the size of bacteria. In fact, they were originally mistaken for bacteria following their discovery in 1992, when scientists were researching Legionella pathogens in water. The viruses have been isolated from both fresh and salt water environments. In 2004, researchers characterized a mimivirus isolate from cooling-water towers.1 It was the largest virus known to exist, measuring a whopping 400 nm in diameter (the classic polio virus is under 30 nm in size). Within this large shell is an unusually large amount of viral DNA coding for proteins and enzymes not typically found in viruses.
Previously featured in On Tap (Mysterious Microbe in Water Challenges the Very Definition of a Virus, June 2010), mimiviruses were not seriously considered as waterborne contaminants of concern, primarily due to the fact that little evidence existed linking them to human disease. Anecdotal evidence of an exposed lab worker with pneumonia and increased rates of mimivirus isolates in a group of patients with community-acquired pneumonia and ICU patients in France provided little concrete proof for concern.2 In recent years, however, new evidence has surfaced revealing the possible connection between mimiviruses and human disease.
The outer shell of the viruses mimic animal collagen, which has been shown to elicit an immune response to collagen. Collagen comprises the proteins that make up the various connective tissues in both humans and animals. It is the most abundant protein in mammals—making up about 30 percent of the total body’s protein levels—and is found in tendons, ligaments, cartilage, etc. Recently, researchers have studied responses to mimiviruses in a laboratory mouse model.3 When mice were exposed to mimivirus proteins, they quickly produced antibodies against the foreign substance. This immune response also resulted in an antibody attack against the mouse collagen, leading to joint inflammation. In other words, exposure to mimivirus resulted in arthritis in the mice.
Exposure evidence
Mimiviruses are widespread in the environment and thus, humans are constantly exposed. Although these viruses grow inside other water-based amoeba, this still does not offer protection from exposure. Approximately one-third (30 percent) of us exhibit physiological evidence of mimivirus exposure at some point in our life.3 This is evidenced by blood serum tests for the virus antibodies. Serum antibody levels are significantly higher for persons with rheumatoid arthritis (36 percent). Another mimivirus protein was found to elicit an immune response in six percent of healthy individuals, compared to 22 percent in rheumatoid arthritis patients. According to the study published in the Journal of Virology (Shah, et al. 2014), “….environmental exposure to mimivirus represents a risk factor in triggering auto-immunity to collagens.”
As an auto-immune disease, rheumatoid arthritis occurs when the body’s immune system mistakenly attacks its own joints. The immune response is identical to that designed to protect the body against invading foreign substances (like bacteria and viruses) and induce a protective immune response. Rheumatoid arthritis is an auto-immune disease affecting more than 1.5 million Americans.4 It is a chronic and painful ailment that may occur intermittently or persist with regular occurrence. Joint inflammation is the primary symptom. When and where joint inflammation flares can be difficult to predict, leaving physicians uncertain regarding the triggers of the disease. Intermittent and chronic immune response indicates the presence of a virus, but lack of previous symptomology conversely indicates a mistaken autoimmune response—or does it? If mimiviruses are present in the body, perhaps the body’s response is not a mistake and symptoms could be alleviated by minimizing the foreign substance exposure rates.
Environmental sources
The first step in reducing mimivirus exposures is to identify their environmental niches. Water ingestion is thought to be the most frequent route of exposure to mimiviruses. Once ingested, the viruses are likely captured by immune cells lining the gut. Respiratory routes of entry have also been identified where the virus can be taken in by immune cells in the lung. Mimivirus infection has also been related to pneumonia but this is rare given that the viruses do not replicate in human cells. Rather, mimiviruses initiate health effects more indirectly via the side effects of an immune response.
Overall, mimiviruses are expected to be prevalent wherever their amoebic hosts persist. With a life cycle similar to Legionella, now the number-one cause of waterborne outbreaks in the US, mimiviruses are likely present in cooling towers, misters, water heaters and household or commercial building premise plumbing. Little is known about the fate and transport of mimiviruses in our drinking and recreational water systems. We also know little about effective treatment measures to reduce their prevalence in both source and tap water supplies. More information is needed regarding chlorine disinfectant efficacy, amoebic host protection and effective POU devices to minimize human exposures.
Exposure prevention
No cure exists for rheumatoid arthritis. Persons who suffer from the condition rely on a number of medications to manage the symptoms. Physical activity, weight management, proper nutrition and rest are typical self-care recommendations to minimize flare-ups as well. Given that water-based mimiviruses can persist in source and treated drinking waters and that these organisms have been associated with rheumatoid arthritis, it seems prudent to add drinking purified water to the list of self-care options. While more research is needed on effective mimivirus mitigation, POU technologies designed to eliminate viral, bacterial and amoebic organisms are likely to reduce the large mimiviruses as well.
References
- Raoult, D.; Audic, S.; Robert, C. et al. “The 1.2-megabase genome sequence of Mimivirus,” Science, vol. 306, pp. 1,344-1,350, 2004.
- Raoult, D.; La Scola, B. and Birtles, R. “The discovery and characterizaitn of mimivirus, the largest known virus and putative pneumonia agent,” Clinical Infectious Diseases, vol. 45, no. 1, pp. 95-102, 2007.
- Shah, N.; Hülsmeier, A.J.; Hochhold, N.; Neidhart, M. et al. “Exposure to Mimivirus Collagen Promotes Arthritis,” Journal of Virology, vol. 88, no. 2, pp. 838-845, 2014.
- Arthritis Foundation, “Rheumatoid arthritis,” The Arthritis Foundation, 2014. [Online]. Available: www.arthritis.org/conditions-treatments/disease-center/rheumatoid-arthritis/. [Accessed 14 01 2014].
About the author
Dr. Kelly A. Reynolds, Associate Professor at the University of Arizona College of Public Health holds a Master of Science Degree in public health (MSPH) from the University of South Florida and a doctorate in microbiology from the University of Arizona. Reynolds is WC&P’s Public Health Editor and a former member of the Technical Review Committee. She may be contacted at [email protected]