Virus Hunters Stalk Through Genome and ID New Disease Associated Viral Family

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Scientists at the University of Pennsylvania Perelman School of Medicine have identified a previously unknown family of small circular DNA viruses that they claim represents the second most abundant DNA virus in the human lung and mouth. The new virus family has been given the name Redondoviridae—from the Spanish word “redondo”, which means round.

The team’s studies found elevated levels of redondovirus DNA in lung specimens from critically ill patients in intensive care units, and also in mouth samples from patients with untreated gum disease. Viral levels in the gum disease patients declined after they received treatment for their periodontitis.

Research leads Frederic D. Bushman, PhD, chair of the department of microbiology, and Ronald G. Collman, MD, a professor of pulmonary, allergy and critical care, and colleagues report on their discoveries in Cell Host Microbe. “These results suggest that redondoviruses colonize human oro-respiratory sites and can bloom in several human disorders,” they concluded in their paper, which is titled “Redondoviridae, a Family of Small, Circular DNA Viruses of the Human Oro-Respiratory Tract Associated with Periodontitis and Critical Illness.”

Virus Hunting (IMAGE)
New sequencing techniques are uncovering a world of new viruses. [Penn Medicine]

Viruses are “the most abundant biological entities on Earth,” the authors wrote, but historically it has been hard to identify new types of virus in populations, such as those harbored in our bodies—the human virome—if their sequences aren’t similar to those already held in reference databases. “New sequencing techniques have helped us uncover a world of new viruses,” said Bushman. “However, the majority of the sequence data we have so far remains unclassified, leaving us much work to do in order to better understand the human virome and how these new species may be associated with illness.”

The Perelman School of Medicine team’s previous analyses of bronchoalveolar lavage (BAL) samples from two organ donors had identified short stretches of DNA that were similar to those of an uncharacterized pig virus. For their newly reported work, the team queried metagenomic datasets from multiple BAL samples, and were able to construct additional complete redondovirus genomes. “Assembly of shotgun metagenomic reads yielded complete circular genomes, which were then used to interrogate our collection of lung virome samples, allowing us to identify seven genomes,” they stated. “These genomes were then used as alignment targets to interrogate publicly available datasets. Twelve more samples had sufficient coverage of redondovirus sequences to allow assembly, yielding 19 complete genomes.”

The researchers next verified that the newly identified viruses didn’t originate from environmental contamination of clinical samples or reagents used in the laboratory, and that they were also not bacteriophages—viruses that infect bacteria. Subsequent analysis of metagenomics sequence datasets from more than 7,500 samples held in 173 datasets covering 51 different organisms and environments indicated that the redondovirus family was found exclusively in humans, and was localized to the human oral cavity and lung, although rarely the viral DNA was also found in gut samples. “Redondoviruses were not found in other animals, fresh water, marine, or soil samples (1,087 non-human biological samples) nor in laboratory reagents (144 contamination control sample),” the researchers stated. “We thus conclude that redondoviruses are authentically present in the human oro-respiratory tract… We cannot rule out that redondoviruses colonize other animal species, although thus far we only identified hits in human samples.”

A large proportion of redondovirus-positive samples were from studies that had included patients with periodontal disease, and the team found that redondovirus DNA levels were higher in individuals with gum disease prior to treatment, and then fell after treatment. “Thus, we conclude that redondoviruses are associated with periodontitis in multiple studies and that levels are reduced with effective treatment,” they wrote. “The role of redondoviruses in periodontitis warrants further study.” Interestingly, direct qPCR analysis of lung samples from 60 healthy adults and 69 critically ill individuals indicated that although redondoviruses were present in healthy people, viral levels were also elevated in the critically ill patients.

“Here, we introduce Redondoviridae, a family of small, circular DNA viruses discovered in metagenomic sequence data, which is found selectively in human lung and oro-pharyngeal samples,” the scientists commented. “Of the DNA viruses we surveyed in 20 human virome datasets, redondoviruses were the second most abundant, exceeded only by anelloviruses.

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