UK DAILY MAIL reporting USA Nat Acad.Science on VIRUS ATCV-1

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice

1. Robert H. Yolken^a,¹,
2. Lorraine Jones-Brando^a,
3. David D. Dunigan^b,
4. Geetha Kannan^c,
5. Faith Dickerson^d,
6. Emily Severance^a,
7. Sarven Sabunciyan^a,
8. C. Conover Talbot, Jr.^e,
9. Emese Prandovszky^a,
10. James R. Gurnon^b,
11. Irina V. Agarkova^b,
12. Flora Leister^a,
13. Kristin L. Gressitt^a,
14. Ou Chen^a,
15. Bryan Deuber^a,
16. Fangrui Ma^b,
17. Mikhail V. Pletnikov^c, and
18. James L. Van Etten^b,¹

Author Affiliations

1. Contributed by James L. Van Etten, October 3, 2014 (sent for review August 9, 2014; reviewed by Joram Feldon and Allan V. Kalueff)

Significance

Human mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.

Abstract

Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being documented in oropharyngeal samples obtained from 40 (43.5%) of 92 individuals. The presence of ATCV-1 DNA was not associated with demographic variables but was associated with a modest but statistically significant decrease in the performance on cognitive assessments of visual processing and visual motor speed. We further explored the effects of ATCV-1 in a mouse model. The inoculation of ATCV-1 into the intestinal tract of 9–11-wk-old mice resulted in a subsequent decrease in performance in several cognitive domains, including ones involving recognition memory and sensory-motor gating. ATCV-1 exposure in mice also resulted in the altered expression of genes within the hippocampus. These genes comprised pathways related to synaptic plasticity, learning, memory formation, and the immune response to viral exposure.

Robert H. Yolken, M.D.

Professor
Pediatric Infectious Disease

Director
Developmental Neurovirology

Specialty:

Infectious Diseases

Location(s):

The Johns Hopkins University School of Medicine
Stanley Division of Developmental Neurovirology
Blalock 1105
600 N. Wolfe Street
Baltimore, MD 21287-4933

Education:

Medical School:
Harvard Medical School

Residency:      
Yale New Haven Hospital

Special Interests:

Neurovirology
Schizophrenia,
Schizophrenia risks,
Biopolar Disorder
Role of Perinatal Infections in Subsequent Brain Development

Biography:

Former chief of Pediatric Infectious Diseases, Robert H. Yolken, the Theodore and Vada Stanley Distinguished Professor of Neurovirology in Pediatrics at Johns Hopkins, chairs the Division of Pediatric Neurovirology the nation’s first pediatric research center designed to investigate links between severe mental illness (including schizophrenia and manic depressive disorders) and early childhood viral infections. He and his research colleagues speculate that a virus invades the brain and then lies dormant for years before triggering the onset of schizophrenia or manic depressive illness in adolescence and young adulthood. They are investigating as possible viral triggers herpes, influenza A and B, and the Toxoplasma gondii parasite, which is carried by cats and farm animals. They believe that in the future antiviral medications might be developed to treat or prevent schizophrenia in some individuals.
The overall goal of the research laboratory is to develop a training and research program devoted to the elucidation of the role of infection and immunity in the etiology of schizophrenia and bipolar disorders. A Interests also include elucidating the role of perinatal infections in subsequent brain development.

A professor in the Division of Pediatric Infectious Disease at Hopkins Children’s, Yolken trained at Harvard, Yale and the National Institutes of Health (NIH) before joining the Hopkins faculty in 1979.
Phone: 410-614-0004
Fax: 410-955-3723
Email: yolken@mail.jhmi.edu