Association of autism with polyomavirus infection in postmortem brains

Abstract

Autism is a highly heritable behavioral disorder. Yet, two decades of genetic investigation have unveiled extremely few cases that can be solely explained on the basis of de novo mutations or cytogenetic abnormalities. Vertical viral transmission represents a nongenetic mechanism of disease compatible with high parent-to-offspring transmission and with low rates of disease-specific genetic abnormalities. Vertically transmitted viruses should be found more frequently in the affected tissues of autistic individuals compared to controls. Our initial step was thus to assess by nested polymerase chain reaction (PCR) and DNA sequence analysis the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), human herpes virus 6 (HHV6), BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) in genomic DNA extracted from postmortem temporocortical tissue (Brodmann areas 41/42) belonging to 15 autistic patients and 13 controls. BKV, JCV, and SV40 combined are significantly more frequent among autistic patients compared to controls (67% versus 23%, respectively; P < .05). The majority of positives yielded archetypal sequences, whereas six patients and two controls unveiled single-base pair changes in two or more sequenced clones. No association is present with the remaining viruses, which are found in relatively few individuals (N <or= 3). Also polyviral infections tend to occur more frequently in the brains of autistic patients compared to controls (40% versus 7.7%, respectively; P = .08). Follow-up studies exploring vertical viral transmission as a possible pathogenetic mechanism in autistic disorder should focus on, but not be limited to, the role of polyomaviruses.

The Neurobiology of Lipid Metabolism in Autism Spectrum Disorders

“…Moreover, polyomavirus genome was detected in postmortem brain tissues from individuals with autism, indicating the presence of infection in the brain of these patients [239] . Although the molecular mechanisms by which viral infections contribute to the pathology of autism via PGE 2 signaling are still largely unknown and often inconclusive, the animal models provide some indirect evidence that altered immune responses due to infections might contribute to the development of autism.…”

The Role of the Immune System in Autism Spectrum Disorder

“…Varying reports have also implicated measles and mumps (Deykin and MacMahon, 1979), cytomegalovirus (Libbey et al, 2005), polyomaviruses (Lintas et al, 2010), and influenza (Atladottir et al, 2012;Deykin and MacMahon, 1979;Shi et al, 2003;Zhang et al, 2010) in the incidence of ASD. Some studies suggest fever as a correlate (Atladottir et al, 2012), with this risk potentially tempered by anti-fever medications, such as Advil, Tylenol, or Nyquil (Zerbo et al, 2013).…”

“…Given the diversity of infections that show a connection to the spectrum of autism disorders (Boksa, 2010;Libbey et al, 2005), as well as evidence from MIA models that reaction to infection rather than infection itself may lead to autismrelated symptoms (Shi et al, 2003), a possible common etiology may be the influence of the immune system (Gottfried et al, 2015;Lintas et al, 2010;Zhang et al, 2010). Cytokines, small cell-signaling proteins that act as immunomodulatory and endocrine messengers, have been implicated throughout the process of CNS development (Boulanger, 2009;Jones and Thomsen, 2013).…”

Exploring the Potential Role of Inflammation as an Etiological Process in ASD

“…In a study on the effects of polyomavirus infection on postmortem brains, the temporocortical regions of 15 adults with ASD and 13 without underwent DNA extraction (Lintas et al 2010). Polyomaviruses are small viruses that are typically acquired during childhood.…”

“…Through polymerase chain reaction (PCR) and DNA sequence analysis, it was observed that heightened combined levels of BKV, JCV, and SV40 were significantly more frequent (67 %) in postmortem brains of individuals having had ASD than in controls (23 %). The vertical viral transmission hypothesis is thought to be involved in this pathway, using a mechanism in which the virus camouflages itself from the body's detection as a genetic transmission mode (Lintas et al 2010). More research is needed to determine the relation of the vertical viral transmission hypothesis in vitro with the manifestation of polyomavirus infections in postmortem brains of autistic individuals.…”