Abstract
Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.
References
Aswad, A., & Katzourakis, A. (2017). A novel viral lineage distantly related to herpesviruses discovered within fish genome sequence data. Virus Evolution, 3(2), vex016.
Binstock, T. (2001). Intra-monocyte pathogens delineate autism subgroups. Medical Hypotheses, 56(4), 523–531.
Carroll, D., Daszak, P., Wolfe, N. D., Gao, G. F., Morel, C. M., Morzaria, S., et al. (2018). The global virome project. Science, 359(6378), 872–874.
Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Child Schizophrenia, 1(1), 33–47.
Dong, G. P., Shang, S. Q., Du, L. Z., Yu, X. L., Xu, X. L., Xu, Y. P., & Wu, X. J. (2004). Detection of four human herpesviruses DNA and Virus-specific IgM antibody in blood specimens of infants. Zhonghua Er Ke Za Zhi, 42, 367–370.
El-Dahr, J. M., Binstock, T., & Singh, V. K. (1998). Association of anti-MBP and anti-NAFP antibodies with HHV-6 antibodies in a child with autistic regression. Journal of Allergy and Clinical Immunology, 101(1), S122.
Garofoli, F., Lombardi, G., Orcesi, S., Pisoni, C., Mazzucchelli, I., Angelini, M., et al. (2017). An Italian prospective experience on the association between congenital cytomegalovirus infection and autistic spectrum disorder. Journal of Autism and Developmental Disorders, 47(5), 1490–1495.
Gentile, I., Zappulo, E., Coppola, N., Bonavolta, R., Portella, G., Cernia, D. S., et al. (2013). Prevalence of HHV-6 and HHV-8 antibodies in patients with autism spectrum disorders. In Vivo, 27(6), 843–849.
Gentile, I., Zappulo, E., RIiccio, M. P., Binda, S., Bubba, L., Pellegrinelli, L., et al. (2017). Prevalence of congenital cytomegalovirus infection assessed through viral genome detection in dried blood spots in children with autism spectrum disorders. In Vivo, 31(3), 467–473.
Goodin, D. A. (2012). El virus HHV-6 y su relación con los trastornos del neurodesarrollo. Cuadernos de Neuropsicología/Panamerican Journal of Neuropsychology, 6(2), 85–94.
Grahn, A., Bergström, T., Runesson, J., & Studahl, M. (2016). Varicella-zoster virus (VZV) DNA in serum of patients with VZV central nervous system infections. Journal of Infection, 73(3), 254–260.
Grether, J. K., Croen, L. A., Anderson, M. C., Nelson, K. B., & Yolken, R. H. (2010). Neonatally measured immunoglobulins and risk of autism. Autism Research, 3(6), 323–332.
Gundogdu, A., & Nalbantoglu, U. (2017). Human genome-microbiome interaction: Metagenomics frontiers for the aetiopathology of autoimmune diseases. Microbial Genomics, 3(4), e000112.
Johnson, G., Nelson, S., Petric, M., & Tellier, R. (2000). Comprehensive PCR-based assay for detection and species identification of human herpesviruses. Journal of Clinical Microbiology, 38(9), 3274–3279.
Le Couteur, A., Rutter, M., Lord, C., Rios, P., Robertson, S., Holdgrafer, M., et al. (1989). Autism diagnostic interview: A standardized investigator-based instrument. Journal of Autism and Developmental Disorders, 19(3), 363–387.
Libbey, J. E., Sweeten, T. L., McMahon, W. M., & Fujinami, R. S. (2005). Autistic disorder and viral infections. Journal of Neurovirology, 11(1), 1–10.
Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., & Schopler, E. (1989). Austism diagnostic observation schedule: A standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders, 19(2), 185–212.
Mahic, M., Mjaaland, S., Bøvelstad, H. M., Gunnes, N., Susser, E., Bresnahan, M., et al. (2017). Maternal immunoreactivity to herpes simplex virus 2 and risk of autism spectrum disorder in male offspring. mSphere, 2(1), e00016–e00017.
Moteki, H., Isaka, Y., Inaba, Y., Motobayashi, M., Nishio, S. Y., Ohira, S., et al. (2018). A rational approach to identifying newborns with hearing loss caused by congenital cytomegalovirus infection by dried blood spot screening. Acta Oto-Laryngologica, 7, 1–5.
Nicolson, G. L., Gan, R., Nicolson, N. L., & Haier, J. (2007). Evidence for Mycoplasma ssp., Chlamydia pneunomiae, and human herpes virus-6 coinfections in the blood of patients with autistic spectrum disorders. Journal of Neuroscience Research, 85(5), 1143–1148.
Odell, D., Maciulis, A., Cutler, A., Warren, L., McMahon, W. M., Coon, H., et al. (2005). Confirmation of the association of the C4B null allele in autism. Human Immunology, 66(2), 140–145.
Readhead, B., Haure-Mirande, J. V., Funk, C. C., Richards, M. A., Shannon, P., Haroutunian, V., et al. (2018). Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron, 99(1), 64.e7–82.e7.
Reyes, A., Semenkovich, N. P., Whiteson, K., Rohwer, F., & Gordon, J. I. (2012). Going viral: Next-generation sequencing applied to phage populations in the human gut. Nature Reviews Microbiology, 10(9), 607.
Roux, S., Hallam, S. J., Woyke, T., & Sullivan, M. B. (2015). Viral dark matter and virus–host interactions resolved from publicly available microbial genomes. eLife, 4, e08490.
Torres, A. R., Westover, J. B., Gibbons, C., Johnson, R. C., & Ward, D. C. (2012). Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism. Brain, Behavior, and Immunity, 26(7), 1122–1127.
Wakefield, A. J., Fox, J. D., Sawyerr, A. M., Taylor, J. E., Sweenie, C. H., Smith, M., et al. (1992). Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn’s disease using the nested polymerase chain reaction. Journal of Medical Virology, 38(3), 183–190.
Windham, G. C., Anderson, M. C., Croen, L. A., Smith, K. S., Collins, J., Grether, J. K. (2011). Birth prevalence of autism spectrum disorders in the San Francisco Bay Area by demographic and ascertainment source characteristics. Journal of Autism and Developmental Disorders, 41(10), 1362–1372.
Acknowledgments
This research was supported by a grant from the Jonty Foundation. The authors are grateful to Drs. Robert Yolken and Martin Kharrazi for their thoughtful comments on the manuscript. We also thank Dr. William M. McMahon and the University of Utah Autism Research Program for their assistance in ascertainment of samples.
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TS conceived of the study, participated in its design, carried out the assays and drafted the manuscript; AT helped conceive the study, participated in its design, contributed to development of laboratory procedures and helped draft the manuscript; LC and GW coordinated the ascertainment and characterization of blood spot sample subjects and helped draft the manuscript. JO and ES provided clinical samples and diagnosed study subjects. All authors read and approved the final manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
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Informed consent was obtained from all individual participants included in the study.
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Sweeten, T.L., Croen, L.A., Windham, G.C. et al. Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls. J Autism Dev Disord 49, 410–414 (2019). https://doi.org/10.1007/s10803-018-3691-x
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DOI: https://doi.org/10.1007/s10803-018-3691-x