Skip to main content

Advertisement

SpringerLink
Log in

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

  • Brief Report
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

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.

    Article  Google Scholar 

  • Binstock, T. (2001). Intra-monocyte pathogens delineate autism subgroups. Medical Hypotheses, 56(4), 523–531.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Chess, S. (1971). Autism in children with congenital rubella. Journal of Autism and Child Schizophrenia, 1(1), 33–47.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Gundogdu, A., & Nalbantoglu, U. (2017). Human genome-microbiome interaction: Metagenomics frontiers for the aetiopathology of autoimmune diseases. Microbial Genomics, 3(4), e000112.

    Article  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Center for Persons with Disabilities and Department of Biology, Utah State University, Logan and Brigham City, UT, USA

    Thayne L. Sweeten

  2. Division of Research, Kaiser Permanente of Northern California, Oakland, CA, USA

    Lisa A. Croen

  3. Division of Environmental and Occupational Disease Control, California Department of Public Health, Richmond, CA, USA

    Gayle C. Windham

  4. Center for Persons with Disabilities, Utah State University, Logan, UT, USA

    J. Dennis Odell & Anthony R. Torres

  5. Oregon Health & Science University, Portland, OR, USA

    E. Gene Stubbs

Authors
  1. Thayne L. Sweeten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa A. Croen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gayle C. Windham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Dennis Odell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Gene Stubbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anthony R. Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Thayne L. Sweeten.

Ethics declarations

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-018-3691-x

Keywords

Search

Navigation