A mysterious new virus isolated in Vietnamese patients with severe brain infections has researchers concerned about the possibility of an undetected infectious disease affecting the central nervous system of vulnerable populations.

The virus, tentatively dubbed CyCV-VN, is a newly identified species that belongs to the genus known as Cyclovirus. Cycloviruses have been found in sheep, cows, chimpanzees, bats, cockroaches, and dragonflies, as well as in humans, but have not previously been linked to any human or animal diseases. Infectious disease viruses in the larger family Circoviridae have only been found in pigs and birds.

"We don't yet know whether this virus is responsible for causing the serious brain infections we see in these patients, but finding an infectious agent like this in a normally sterile environment like the fluid around the brain is extremely important," said Dr. Rogier van Doorn, a clinical microbiologist at the Oxford University Clinical Research Unit in Vietnam, in a news release.

"We need to understand the potential threat of this virus to human and animal health."

Researchers have provided details on the new virus in a recent report.

What Causes Central Nervous System Infections?

Brain infections can be caused by a wide variety of viral, bacterial, parasitic, and fungal pathogens, and are often fatal or crippling, especially for young people or those with weakened immune systems.

Such conditions are particularly prevalent in tropical regions like Vietnam, and can be difficult for doctors to treat or even identify because relatively little is known about what causes the majority of cases.

A team of Vietnamese, British, and Dutch researchers investigated the high rate of acute central nervous system infections in Vietnam by collecting cerebrospinal fluid samples from thousands of undiagnosed patients suspected of having conditions like viral encephalitis.

Decoding the Cyclovirus Genome

DNA analysis of the fluid samples resulted in 161,000 intriguing sequences, and further parsing indicated that a specific cyclovirus sequence was present in two index patients, an adult and a child.

Using a method called inverse polymerase chain reaction (iPCR), the researchers amplified that sequence to construct the entire virus genome, revealing a never-before-seen cyclovirus that they called CyCV-VN.

The fully sequenced genome allowed them to detect CyCV-VN in cerebrospinal fluid samples from a total of 28 out of 644 patients with suspected central nervous system infections, but not in any samples from 122 patients with non-infectious brain disorders like multiple sclerosis — suggesting a possible infectious disease virus.

"The detection of CyCV-VN in a usually sterile material like cerebrospinal fluid is remarkable and may point to a pathogenic role of this virus as a single or a co-infecting pathogen," said first author Dr. Le Van Tan in the team's press statement.

CyCV-VN Present in Livestock, Wide Variety of Vietnamese People

The 28 infected patients came from people ranging in age from infancy to over 60 years, who lived in seven different provinces of southern and central Vietnam, indicating that the cyclovirus has a wide geographic range and no specific age targets.

The fluid samples were collected over a ten-year period ending in 2009, suggesting that the virus did not emerge suddenly.

The researchers noted in the paper that CyCV-VN seems to have a low mortality in infected patients — a reassuring sign — though more outcome monitoring is necessary to determine its effects.

The cyclovirus was also found in eight out 188 fecal samples from healthy Vietnamese children, as well as in over half of pigs, ducks, and chickens tested in Dong Thap province, the home of the first patient in whom CyCV-VN was detected.

"The evidence so far seems to suggest that CyCV-VN may have crossed into humans from animals, another example of a potential zoonotic infection," said Tan.

Based on its presence in both animals and fecal samples, the researchers suggest possible food-borne or oral-fecal transmission routes from animal livestock to humans.

No Proof That Cyclovirus Causes Brain Infections

There's no need to panic about an infectious outbreak quite yet, researchers said. Although the cyclovirus has only been found in people with brain infections thus far, it's not clear that CyCV-VN actually caused those infections.

"While detection of this virus in the fluid around the brain is certainly remarkable, it could still be that it doesn't cause any harm," said Tan. "Addressing the question of causation requires extensive effort."

In the paper, the researchers concluded that while ongoing study is vital to discount the possibility of a contagious pathogen, the general public should keep in mind the case of a leukemia virus that was recently linked in patients with prostate cancer and chronic fatigue syndrome, only to be disassociated from each condition last year.

The next step in the team's research is to grow the cyclovirus in a lab, which would help them develop an antibody test for assessing the presence of CyCV-VN in patients.

They are also working with scientists across Southeast Asia to determine whether CyCV-VN has spread geographically outside Vietnam.

 

Source: Tan LV, van Doorn HR, Nghia HDT, et al. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections. mBio. 2013.