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

Robert H. Yolken, Lorraine Jones-Brando, David D. Dunigan, Geetha Kannan, Faith Dickerson, Emily Severance, Sarven Sabunciyan, C. Conover Talbot, Emese Prandovszky, James R. Gurnon, Irina V. Agarkova, Flora Leister, Kristin L. Gressitt, Ou Chen, Bryan Deuber, Fangrui Ma, Mikhail V. Pletnikov, James L. Van Etten

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)16106-16111
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number45
DOIs
StatePublished - Nov 11 2014

Fingerprint

Chlorella
Cognition
DNA Viruses
Viruses
Phycodnaviridae
Sensory Gating
Metagenomics
Chlorophyta
Neuronal Plasticity
Sequence Homology
Pharynx
Psychiatry
Hippocampus
Demography
Learning
Gene Expression
Polymerase Chain Reaction
DNA

Keywords

  • chlorovirus ATCV-1
  • cognitive functioning
  • infection
  • metagenomic sequencing
  • oropharyngeal virome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice. / Yolken, Robert H.; Jones-Brando, Lorraine; Dunigan, David D.; Kannan, Geetha; Dickerson, Faith; Severance, Emily; Sabunciyan, Sarven; Talbot, C. Conover; Prandovszky, Emese; Gurnon, James R.; Agarkova, Irina V.; Leister, Flora; Gressitt, Kristin L.; Chen, Ou; Deuber, Bryan; Ma, Fangrui; Pletnikov, Mikhail V.; Van Etten, James L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 45, 11.11.2014, p. 16106-16111.

Research output: Contribution to journalArticle

Yolken, Robert H. ; Jones-Brando, Lorraine ; Dunigan, David D. ; Kannan, Geetha ; Dickerson, Faith ; Severance, Emily ; Sabunciyan, Sarven ; Talbot, C. Conover ; Prandovszky, Emese ; Gurnon, James R. ; Agarkova, Irina V. ; Leister, Flora ; Gressitt, Kristin L. ; Chen, Ou ; Deuber, Bryan ; Ma, Fangrui ; Pletnikov, Mikhail V. ; Van Etten, James L. / Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 45. pp. 16106-16111.
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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.",
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AU - Yolken, Robert H.

AU - Jones-Brando, Lorraine

AU - Dunigan, David D.

AU - Kannan, Geetha

AU - Dickerson, Faith

AU - Severance, Emily

AU - Sabunciyan, Sarven

AU - Talbot, C. Conover

AU - Prandovszky, Emese

AU - Gurnon, James R.

AU - Agarkova, Irina V.

AU - Leister, Flora

AU - Gressitt, Kristin L.

AU - Chen, Ou

AU - Deuber, Bryan

AU - Ma, Fangrui

AU - Pletnikov, Mikhail V.

AU - Van Etten, James L.

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N2 - 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.

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