New test can detect any virus in humans or animals

Name that virus! A new genomic test is able to detect any virus found in humans or animals, even at low levels, according to a September 22, 2015 online report in Genome Research. More than this, the test can identify the virus’s taxonomy, strain, virulence, and drug resistance.

The test builds on metagenomic shotgun sequencing (MSS), a genomic testing process that comprehensively evaluates all genes from all organisms present in a given complex sample. However, MSS can lack sensitivity and may yield insufficient data for detailed analysis.

So, researchers in this investigation created a targeted sequence capture panel, called ViroCap, which condensed nearly 1 billion base pairs (bp) of viral reference sequence into less than 200 million bp of unique, representative sequence suitable for targeted sequence capture.

“With this test, you don’t have to know what you’re looking for,” said the study’s senior author, Gregory Storch, MD, the Ruth L. Siteman Professor of Pediatrics at Washington University School of Medicine in St. Louis, MO, where the technology was developed. “It casts a broad net and can efficiently detect viruses that are present at very low levels. We think the test will be especially useful in situations where a diagnosis remains elusive after standard testing or in situations in which the cause of a disease outbreak is unknown.”

ViroCap could be used, for instance, to detect outbreaks of deadly viruses such as Ebola, Marburg, and severe acute respiratory syndrome (SARS), as well as routine viruses, including rotavirus and norovirus.

The authors noted that this new test is just as sensitive as the gold-standard polymerase chain reaction (PCR) assay, although even the most expansive PCR assays can only screen for up to about 20 similar viruses at the same time.

In this study, the researchers compared the new test with conventional MSS testing in two sets of biological samples—one set from samples submitted to a diagnostic virology laboratory and the other derived from samples collected in a study of fever in children.

In the first, MSS testing detected viruses in 10 of 14 patients. But ViroCap found those 10 plus 4 additional viruses that MSS testing had missed. These were common, everyday viruses—influenza B, parechovirus, herpes virus 1, and varicella-zoster virus. In a second group of children with unexplained fevers, standard MSS testing detected 11 viruses, but the new test found those and another 7 viruses, including human adenovirus B type 3A.

In the two experiments combined, MSS detected 21 viruses compared with 32 detected by ViroCap—a 52% increase.

“The test is so sensitive that it also detects variant strains of viruses that are closely related genetically,” said corresponding author Todd Wylie, ‎Director of Microbial Genomics Computing at Washington University School of Medicine. “Slight genetic variations among viruses often can’t be distinguished by currently available tests, and complicate physicians’ ability to detect all variants with one test.”

In addition, the test can simultaneously provide immediate characterization of a virus, including taxonomic assignment, strain typing, virulence characteristics, and antiviral drug resistance genotyping. For example, the study showed that while standard MSS testing identified influenza A, the new test indicated that the virus was the particularly harsh H3N2 subtype.

As novel viruses are discovered, their genetic sequences could be easily added to the test’s panel, Dr. Storch said.

“It also may be possible to modify the test so that it could be used to detect pathogens other than viruses, including bacteria, fungi and other microbes, as well as genes that would indicate the pathogen is resistant to treatment with antibiotics or other drugs,” said co-author Kristine Wylie, PhD, Assistant Professor of Pediatrics at Washington University School of Medicine.

For now, the researchers will conduct additional research to validate the accuracy of the test, so ViroCap may not be clinically available for several years. In the meantime, the researchers are making the technology they developed publicly available to scientists and clinicians worldwide, for the benefit of patients and research.