title: Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.
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.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, jvanetten1@unl.edu rhyolken@gmail.com.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Jones-Brando
authors.affiliation: Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and.
authors.forename: David D
authors.initials: DD
authors.lastname: Dunigan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, and.
authors.forename: Geetha
authors.initials: G
authors.lastname: Kannan
authors.affiliation: Department of Psychology, Sheppard Pratt Health System, Baltimore, MD 21205.
authors.forename: Faith
authors.initials: F
authors.lastname: Dickerson
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Emily
authors.initials: E
authors.lastname: Severance
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Sarven
authors.initials: S
authors.lastname: Sabunciyan
authors.affiliation: Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
authors.forename: C Conover
authors.initials: CC
authors.lastname: Talbot
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Emese
authors.initials: E
authors.lastname: Prandovszky
authors.affiliation: Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and.
authors.forename: James R
authors.initials: JR
authors.lastname: Gurnon
authors.affiliation: Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Agarkova
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Flora
authors.initials: F
authors.lastname: Leister
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Gressitt
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Ou
authors.initials: O
authors.lastname: Chen
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics.
authors.forename: Bryan
authors.initials: B
authors.lastname: Deuber
authors.affiliation: Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and.
authors.forename: Fangrui
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Psychiatry and Behavioral Sciences, and.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Pletnikov
authors.affiliation: Nebraska Center for Virology and Department of Plant Pathology, University of Nebraska, Lincoln, NE 68583-0900; and jvanetten1@unl.edu rhyolken@gmail.com.
authors.forename: James L
authors.initials: JL
authors.lastname: Van Etten
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002708:Chlorella / Q000821:virology*; D003071:Cognition; D005260:Female; D006801:Humans; D007830:Larynx / Q000821:virology*; D008297:Male; D008568:Memory; D051379:Mice; D009036:Moths / Q000821:virology*; D017862:Phycodnaviridae
keywords: chlorovirus ATCV-1; cognitive functioning; infection; metagenomic sequencing; oropharyngeal virome