First published April 12 2011
Let’s talk about the link between our fellow travelers (all the bacteria, viruses and other organisms residing with us – actually mostly in us). Biological psychiatry is just coming to terms with the microbiome/microbiota, and its influence on the function of the brain. As we collectively try to understand the influence of this unseen influence on the human condition, we cannot forget the influence of our shared viral travelers. The obvious viruses, herpes as an example, exist with us from our first encounter until the end of our days. But many viruses are capable of lifelong cohabitation with humans.
The most obvious viruses are; Human Papilloma (HPV), Herpes Simplex (HSV), Cytomegalovirus (CMV), Hepatitis (Hep B and C as well as others), Human Immunodeficiency (HIV), Epstein Barr (EBV – mononucleosis), Varicella (chickenpox), Measles, Polio, SV40, BK and JC. XMRV is a potential new addition to this list, and despite its controversy I believe it is a true human pathogen. My belief in XMRV as a necessary member of the list is based on both PCR and anti-XMRV antibodies, not merely XMRV PCR (genetic) material.
Some of these have a potential legacy with autism. We discussed this in an earlier post. But this viral community interfaces with the bacteria community in complex and incompletely understood ways.
The mind-body-microbial continuum.
Our understanding of the vast collection of microbes that live on and inside us (microbiota) and their collective genes (microbiome) has been revolutionized by culture-independent “metagenomic” techniques and DNA sequencing technologies. Most of our microbes live in our gut, where they function as a metabolic organ and provide attributes not encoded in our human genome. Metagenomic studies are revealing shared and distinctive features of microbial communities inhabiting different humans. A central question in psychiatry is the relative role of genes and environment in shaping behavior. The human microbiome serves as the interface between our genes and our history of environmental exposures; explorations of our microbiomes thus offer the possibility of providing new insights into our neurodevelopment and our behavioral phenotypes by affecting complex processes such as inter- and intrapersonal variations in cognition, personality, mood, sleep, and eating behavior, and perhaps even a variety of neuropsychiatric diseases ranging from affective disorders to autism. Better understanding of microbiome-encoded pathways for xenobiotic metabolism also has important implications for improving the efficacy of pharmacologic interventions with neuromodulatory agents.
Dialogues Clin Neurosci. 2011;13(1):55-62.
Gonzalez A, Stombaugh J, Lozupone C, Turnbaugh PJ, Gordon JI, Knight R.
Department of Computer Science, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
Now some critical thinking about GcMAF (the activated Vitamin D3 receptor) and its role or failure in defending us from viral persistence. IF or perhaps better stated SINCE viruses are able to defeat our extremely crafty immune system, the question is how? I won’t presume to claim to understand all the mechanism but let’s divide our discussion into three viral categories: 1) DNA viruses, 2) RNA viruses and 3) retroviruses.
DNA viruses have the unique ability to behave as though they belong to the cell since they are DNA. DNA – unlike RNA which is rapidly broken down and recycled – is conserved by cells because of its genetic blueprint.
RNA viruses (measles, hepatitis etc) must (at least as best we understand things) have some degree of replication to survive. This means if they do not keep making copies at some steady (albeit slow) rate they could not persist since inactive RNA is destroyed by cell enzymes called RNases.
Retroviruses (HIV and XMRV) have a unique twist on this model. They are RNA viruses but they don’t stay RNA viruses. They convert to DNA once inside the cell they are infecting.
From Wikipedia: “A retrovirus is an RNA virus that is replicated in a host cell via the enzyme reverse transcriptase to produce DNA from its RNA genome. The DNA is then incorporated into the host’s genome by an integrase enzyme. The virus thereafter replicates as part of the host cell’s DNA. Retroviruses are enveloped viruses that belong to the viral family Retroviridae.
A special variant of retroviruses are endogenous retroviruses which are integrated into the genome of the host and inherited across generations.”
We have data and observations of an altered microbiome in children with autism, and we have information supporting viral persistence and immune disruption. I doubt these are unrelated events. Frequently we see strong positive effects from treating yeast and bacteria in ASD. If the viral hypothesis is accurate – it is difficult to conceive of how this happens apart from an immune effect.
The likely immune response was always thought of proinflammatory. But what if it more than just upregulating immune responses? What if the gut immune response to the presence of yeast and bacteria actually assists the viral persistence? Is that possible?
The short answer is. I believe both viral persistence and gut microbiome issues are inter-related events in autism.
I think the linkage is driven through widespread and common Vitamin D deficiency combined with production of nagalase by certain infected cells. Nagalase (as we have mentioned before) is an enzyme which digests the sugars off the active D3 receptor (VDR) – effectively neutralizing the immune response. This actions seems to be a required step in viral persistence and cancer development. I am not saying autism is associated with cancer – although I see far to many early onset breast cancers in the mothers of children with autism and there may be a connection to viruses and nagalase.
Stem cells express upregualtion of VDR expression (they have more d3 receptors). Vitamin D regulates the expression of its receptors and has an anti-inflammatory effect. This is especially in pregnancy. See; (J Immunol. 2011 Apr 11. [Epub ahead of print] Vitamin D and the Regulation of Placental Inflammation. Liu NQ, et al.).