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Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16106-11. doi: 10.1073/pnas.1418895111. Epub 2014 Oct 27.

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

Author information

1
Stanley Division of Developmental Neurovirology, Department of Pediatrics, jvanetten1@unl.edu rhyolken@gmail.com.
2
Stanley Division of Developmental Neurovirology, Department of Pediatrics.
3
Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and.
4
Department of Psychiatry and Behavioral Sciences, and.
5
Department of Psychology, Sheppard Pratt Health System, Baltimore, MD 21205.
6
Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
7
Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and jvanetten1@unl.edu rhyolken@gmail.com.

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.

KEYWORDS:

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

PMID:
25349393
PMCID:
PMC4234575
DOI:
10.1073/pnas.1418895111
[Indexed for MEDLINE]
Free PMC Article

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