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

Authors

Robert H. Yolken, Johns Hopkins School of MedicineFollow
Lorraine Jones-Brando, Johns Hopkins School of Medicine
David D. Dunigan, University of Nebraska-LincolnFollow
Geetha Kannan, Johns Hopkins School of Medicine
Faith Dickerson, Sheppard Pratt Health System
Emily Severance, Johns Hopkins School of Medicine
Sarven Sabunciyan, Johns Hopkins School of Medicine
C. Conover Talbot Jr., Johns Hopkins School of Medicine
Emese Prandovszky, Johns Hopkins School of Medicine
James R. Gurnon, University of Nebraska - Lincoln
Irina V. Agarkova, University of Nebraska-LincolnFollow
Flora Leister, Johns Hopkins School of Medicine
Kristin L. Gressitt, Johns Hopkins School of Medicine
Ou Chen, Johns Hopkins School of Medicine
Bryan Deuber, Johns Hopkins School of Medicine
Fangrui Ma, University of Nebraska-LincolnFollow
Mikhail V. Pletnikov, Johns Hopkins School of Medicine
James L. Van Etten, University of Nebraska-LincolnFollow

ORCID IDs

David D. Dunigan

Irina V. Agarkova

James L. Van Etten

Document Type

Article

Date of this Version

11-2014

Citation

PNAS, November 11, 2014, vol. 111, no. 45, pp. 16106-16111.

Comments

Copyright 2014 Yolken et al. Used by permission.

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 visualmotor 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.