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Chlorovirus ATCV-1, a Green Algae Virus, May Slow Human Brain Activity

By Roberta Attanasio

Chlorella viruses, or chloroviruses, infect green algae, single-celled organisms present throughout the world in freshwater ecosystems such as lakes and ponds. Now, it seems that chlorovirues also infect humans, causing changes in cognitive functions — the processes by which information is perceived, registered, stored, retrieved, and used. In other words, chloroviruses influence the ability to acquire and use knowledge. These novel findings — published on line in the scientific journal Proceedings of the National Academy of Sciences (October 27, 2014) — confirm that viruses may be able to jump from one kingdom (plants) to another (animals), something that has been shown only in very few instances. 

Chlorella
Chlorella.  Photo credit: ja:User:NEON, licensed under CC BY-SA 3.0

For the study (Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice), the researchers used throat swabs collected from 92 adults without a psychiatric disorder or serious physical illness. The researchers found that 40 of these adults carried the genetic material of one of the chloroviruses — Acanthocystis turfacea chlorella virus 1, or ATCV-1 for short. They also found that the presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functions. Such a decrease was not associated with age, sex, race, socioeconomic status, cigarette smoking, travel history, or place of birth.

However, this first set of findings did not show “causality” — the ability of ATCV-1 to cause the observed decline in cognitive functions. Thus, the researchers infected mice with the virus. After several months, as expected, the infected mice exhibited signs of cognitive impairment. Moreover, the researchers found that, in both humans and mice, exposure to ATCV-1 was associated with decreases in performance on tasks calling for visual spatial abilities, which are important for everyday life — for example, when using a map or merging into high-speed traffic.

Robert Yolken, one of the study’s authors, said in a press release: “This is a striking example showing that the ‘innocuous’ microorganisms we carry can affect behavior and cognition. Many physiological differences between person A and person B are encoded in the set of genes each inherits from parents, yet some of these differences are fueled by the various microorganisms we harbor and the way they interact with our genes.”

The researchers speculate that the immune system might be involved in the cognitive decline associated with the presence of ATCV-1. In mice infected with the virus, they found changes in several pathways involved in antigen processing and immune cell functioning. These changes were located in the hippocampus, the region of the brain involved in emotions, learning and memory formation. About 35% of the mice mounted an immune response following infection. The researchers propose that a type of chemical messengers called proinflammatory cytokines — which are produced during the activation of the immune system — may affect brain functions, leading to behavioral abnormalities.

Another author of the study, Mikhail Pletnikov, said in an additional press release: “The similarity of our findings in mice and humans underscores the common mechanisms that many microbes use to affect cognitive function in both animals and people. This commonality is precisely what allows us to study the pathologies that these microorganisms fuel and do so in a controlled systematic way.”

Allan Kalueff, the director of the ZENEREI Institute in Slidell, Louisiana, who was not involved in the study, told  of Science News that he suspects other viruses may affect human sensory processing and behavior. He also wondered about health risks to people working in the seafood industry or around waters where they may be exposed to ATCV-1. However, he also said that additional studies are necessary, including animal and plant/algal studies.

16 Comments

  • HJD

    After reading about the effects of ATCV-1, the first thing that came to mind were other viruses that gradually impair one’s cognitive functions such as Rabies virus, and West Nile virus. Also, both West Nile virus & rabies are originally animal viruses that have the ability to infect humans. Not every animal transmitted virus can infect humans, and not even human transmitted virus can infect animals. After a week of being infected with Rabies virus, one may see neurological impairments comparable to ATCV-1. Scientists should perform more studies and test if ATCV-1 antibodies can be created to halt the cognitive impairment after exposure to the virus in inland waters. Once an effective antibody is made, it can be given to people that feel they may have been (or will be) exposed to chlorovirus-infected waters from ponds and lakes. After reading an article written by Dr. Racaniello of Columbia University, scientists can test if other factors, once added with Chlorella viruses, can create a synergistic response leading to the change in one’s cognitive functions. “It is possible that exposure to another factor together with chloroviruses, such as heavy metals, is responsible for the observed cognitive differences (Racaniello)”.

  • Da Chen

    It is interesting to see a virus can infect across kingdoms. As to what have been talked in the blog, there is a possibility that ATCV-1 triggers immune system within the brain and the released proinflammatory cytokines may be the reason of decreasing cognitive function. However, based on a research article published in 2009, ATCV-1 expresses a potassium channel in Xenopus oocytes. I doubt if there is a possibility that ATCV-1 has the same ability to express such protein in brain cells. The signaling within our brain highly depends on the potassium and calcium concentrations across cell membranes. If the virus express the same function protein within mammal’s brain, then the affected potassium concentration across cell membrane may leads to a dysfunction of neurons and causing cognitive decreasing. If the triggered immune response is the cause of decreasing cognitive function, I would like to see whether there is a relation between ATCV-1 infection and cytokine overexpression in future researches. At the same time, I am wondering how the virus is able to trigger chronic inflammation other than being suppressed by the immune system.

  • Paris

    Due to ACTV-1 being actively present in our freshwater ecosystems, its exemplary to suggest that it contaminants our fisheries as well as water supply. Both of these resources possess an unswerving influence on our society’s growth. Being that ACTV-1 disrupting an individuals’ cognitive function, it becomes mind-boggling when thinking about your potential risk of exposure. ACTV-1 thrives in areas where the CO2 composition is bountiful, therefore with the assistance of its catalyst Global Warming, we may potentially recognize an adverse effect, where there will be an increase in ACTV-1 production; resulting in a society that is more susceptible to infection and diseases such as Alzheimer’s and dementia.
    I would question the researchers whether or not if the increase of chlorovirus/ACTV causes an increase in the number of Alzheimer’s and dementia cases reported. If yes, then researchers must methodically contrive a way to control and eradicate the microbiome and virome from its environment. However, prior to this they must first understand the mechanism and how the virus inaugurates these pro inflammatory responses, which in essence causes the decline in cognition. Perhaps researchers should test patients whom suffer from cognitive deprivation, in order to grasp a better understanding of the virus because they may be able to correlate it to the influence of ACTV-1 throughout the individuals life.

  • Corrie

    Reading this post reminds me of brevetoxins released by red tide, an algae bloom caused by dinoflagellate. Brevetoxins have caused an environmental issue in the Gulf of Mexico and other coastal communities. Signs of red tide stress in manatees included seizure, disorientation, incoordination, hyperflexion, muscle fasciculations, flaccid paralysis, and dyspnea. In these biological systems, they act to open voltage gated sodium (Na+) ion channels in cell membranes, leading to Na+ influx into the cell. It was found that brevenal, a brevetoxin antagonist is the first documented case of a toxin-producing organism producing its own antagonist. It acts at a different receptor site on nerve cells than the brevetoxins. Perhaps neurotoxins released or created by chloroviruses is what is causing the cognitive function issues and not the proinflamatory cytokines.

  • sally white

    This is a very interesting finding not only because it points out the dangers posed by viruses until now thought of as non harmful to humans. It also clarifies the controversial subject of the effects of inflammation (which is due to the involvement of the immune system) on cognitive functions. It has been postulated that inflammation in the central nervous system may contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Plus, the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer’s disease and vascular dementia are being studied because there is evidence of correlation. Situations arising because of surgery, cancer chemotherapy, peripheral nerve damage, and heart attack are associated with poor memory, depression, fatigue, and exaggerated responses to pain. What do they have in common? They induce inflammatory responses that lead to cognitive and emotional effects. ATCV-1 may provide a useful model to induce inflammation and study the effects and their mechanisms on things like memory and spatial orientation.

  • JP

    If ACTV-1 is impacting cognitive functions, then there can be a possibility that these microbes are passing through the adaptive immune system and entering into the brain. So, are these viruses taking the form of something else in the adaptive immune system, that is causing the cytokines not to recognize them? If this is the case, researchers should focus on how are these viruses alternating into something else that is causing them to pass the adaptive immune system and causing affects on the cognitive functions in the brain.

    • Claudette C.

      This is the first time I hear a virus can change into something else. It’s a very unlikely possibility, unless you mean that it has variants. And this is the first time I hear that viruses are recognized by cytokines. For what I know, this is not what cytokines do. All together, I think what you’re proposing does not have any possibility of happening.

  • Mark Safry

    I would like to point out that neuroinflammation – the inflammatory response in the central nervous system caused by things such as infectious microbes and toxic metabolites – is the most logical explanation for the findings of the study. The authors of the study are on the right path and should follow up with targeted experiments showing that chloroviruses can cause inflammation of the brain and, therefore, the release of pro-inflammatory cytokines. Pro-inflammatory cytokines are involved in causing depression, Alzheimer’s disease and metabolic disorders as for example Type II diabetes, obesity and cardiovascular diseases. These metabolic disorders, in turn, are associated with a variety of psychiatric illnesses. If we put together everything we come in contact with, willingly or not, and being aware of it or not, that can cause inflammation in the brain, it’s no surprise that there are so many cases of neurodegenerative diseases around. These infectious stimuli along with toxins, chemicals and others, when combined together, are something we can’t control and we respond to with inflammation, trying to protect ourselves, but doing more damage instead. Neuroinflammation is known to promote behavioral changes, thus the findings on the ATCV-1 really deserve further studies. The scientists are working on something novel and important.

  • mgnd88

    These new findings are very interesting. However, as the blog post specifies, the researchers base their conclusions on the presence of the genetic material of the virus in the throat swab samples they analyzed. As of now, they have not demonstrated the presence of infectious virus in the individuals they have tested. I’m just wondering whether or not the finding of the virus genetic material results from the microbial contamination of DNA extraction kits that has been reported during the past few days. An article in BMC Biology (November 11) shows that there is widespread presence of low level contamination in the kits. Even before the study in BMC Biology was published, bacterial DNA had been found in ultrapure water used in labs. I’s possible then that viral DNA can also contaminate the kits. Just another possibility in the interpretation of the ATCV-1 findings that we should be thinking about.

    • Simon Suarez

      I expect this contamination to be recognized as something to worry about in the world of microbiome research. The investigators of the ATCV-1 study described in this blog conducted a metagenomic analysis of DNA extracted from human throat samples, and so your thoughts about results influenced by contamination of the DNA kits used should not been discounted. I believe that when proper negative controls are used, results can receive a safe and fair interpretation. However, the problem of contamination is really widespread. An article published at the end of October in PLOSone reported that DNA from diverse species, including bacteria, plants, and humans, contaminated almost every sample sent through a next-generation sequencer. When unexpected results are found, scientists should always think of possible contamination.

  • PS

    It is fascinating to learn that a virus which is mainly found in algae not only has the ability to infect humans, but also alter our cognitive functions. Since this is such a novel and astonishing finding there are many questions that could arise. ATCV-1 does not seem to have been isolated from the human gut before, but it may be that ATCV-1 is a part of the gut microbiome in only some individuals, and perhaps past sampling have missed them. It has been established that communication between the GI tract and the central nervous system (CNS) does exist; thereby, microbiota can influence the brain. Al-Asmakh et al. noted that mechanisms of communication between the gut and the brain occur via,“neural, immunological, endocrine, and hypothalamic-pituitary-adrenal (HPA) stress axis pathways”.Another study led by Li, Wang reveals a correlation between alterations in gut bacteria and memory and learning behavior in mice. Could ATCV-1 be part of our microbiome and influence cognitive functions by gut-to-brain communication? It will be interesting to read further developments on ATCV-1 and the pathways involved in its effects on the brain.

  • Claudette C.

    Is the presence and/or amount of this virus influenced by the temperature? Will climate change have an effect on the human levels of exposure to this virus?

    • Alex Farmington

      Chlorella thrives in high level of CO2. Thus, the high levels of CO2 caused by climate change lead to increased chlorella growth, so I would think logical to expect more virus if infected chlorella grows rapidly.

      • Lauren C.

        Since the chlorovirus infects freshwater algae and thrives in higher levels of CO2, it would make sense to draw the conclusion that during the summer months, swimmers would be the individuals infected the most. However, what is interesting to me is that those participating in watersports are not the only ones becoming infected with the chlorovirus. Researchers have also found that strong seasonal CO2 fluctuations occur more often in the Northern Hemisphere than the Southern Hemisphere. It would be interesting to see future data that includes the location of individuals that are infected.

  • Ray Kinney

    ATCV-1, if further demonstrated to bring adverse behavioral effects that are health limiting, only adds to a growing list of environmental toxicants that have public health decline effects on populations. BMAA toxin,toxic metals such as lead, methylmercury, and cadmium,and now potentially ATCV-1, can have subtle subclinical effects at chronic low dose that remain under the radar across affected populations. Where this type of exposure overlaps, additive and (likely) synergistic effects, can decrease intelligence and overall health outcomes with very little practical chance of detection etiologic determination.
    Regulatory protections lag far behind epidemiologic clarification and public health risk awareness. Mixtures of low levels of several toxicants are the environmental reality we live in, it’s a ‘buyer beware’world out there, where the deep fringe of medical awareness meets the frontiers of individual existential responsibility for personal wellbeing within a more wholistic public health paradigm. Science needs to quickly extend into this ‘frontier’, providing far better epidemiology and direction for a precautionary approach to inform more responsible product development and subsequent pollutant dispersal.
    If we don’t do this quickly enough ‘nature bats last’ and we won’t adapt to survive well to provide for our great grandchildren.

    • galaxer

      Science does not seem concerned with the precautionary approach. The general idea is to let the damage happen, and then design and carry out studies to fix the damage. Very rarely the damage gets fixed, though!

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