Journal of Autism and Developmental Disorders

, Volume 49, Issue 1, pp 410–414 | Cite as

Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls

  • Thayne L. SweetenEmail author
  • Lisa A. Croen
  • Gayle C. Windham
  • J. Dennis Odell
  • E. Gene Stubbs
  • Anthony R. Torres
Brief Report


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.


Autism spectrum disorder Autism Herpesvirus HHV-6 



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.

Author Contributions

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.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

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.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. Aswad, A., & Katzourakis, A. (2017). A novel viral lineage distantly related to herpesviruses discovered within fish genome sequence data. Virus Evolution, 3(2), vex016.CrossRefGoogle Scholar
  2. Binstock, T. (2001). Intra-monocyte pathogens delineate autism subgroups. Medical Hypotheses, 56(4), 523–531.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Child Schizophrenia, 1(1), 33–47.CrossRefGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 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.Google Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.Google Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. Gundogdu, A., & Nalbantoglu, U. (2017). Human genome-microbiome interaction: Metagenomics frontiers for the aetiopathology of autoimmune diseases. Microbial Genomics, 3(4), e000112.CrossRefGoogle Scholar
  14. 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.PubMedPubMedCentralGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.Google Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Center for Persons with Disabilities and Department of BiologyUtah State UniversityLogan and Brigham CityUSA
  2. 2.Division of ResearchKaiser Permanente of Northern CaliforniaOaklandUSA
  3. 3.Division of Environmental and Occupational Disease ControlCalifornia Department of Public HealthRichmondUSA
  4. 4.Center for Persons with DisabilitiesUtah State UniversityLoganUSA
  5. 5.Oregon Health & Science UniversityPortlandUSA

Personalised recommendations