Researchers probe possible link with kidney disease.
This year is on track to be the worst on record for West Nile virus in the United States. As of 11 September, more than 2,600 new cases, including 118 deaths, had been reported from across the country to the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
Symptoms of the mosquito-borne disease range from none (in most people) to life-threatening brain inflammation, and it can leave survivors with long-term disabilities including paralysis and fatigue. Researchers are now investigating suggestions that even mild infections may leave another lasting burden — kidney disease.
“We are early in our understanding, but this really worries me,” says Kristy Murray, an epidemiologist and clinical researcher at Baylor College of Medicine in Houston, Texas, who has found hints that the virus may persist in the kidney long after the initial infection. This week she is moving her work on the long-term consequences of West Nile to a new biosecurity-level-3 laboratory at nearby Texas Children’s Hospital, where she will explore a link between the virus and kidney disease.
Researchers agree that the claim needs to be investigated. “If Murray’s findings are true, we have to think about what to do with all of these people with mild infections,” says William Reisen, an entomologist at the Center for Vectorborne Diseases at the University of California, Davis. But Murray is also facing scepticism, which she hopes to address in the latest phase of her research.
Murray’s quest began at a meeting of West Nile survivors in Texas in 2009, where a man in his early fifties who had recovered from a 2003 infection announced that he had kidney disease. He was dead within a year. To Murray, his illness brought to mind studies in which researchers had detected and cultured the virus in kidney tissue from laboratory animals long after they were infected with West Nile.
Murray collected urine samples from 25 survivors of West Nile and found that five had viral RNA in their urine well after they had been infected1, suggesting that the virus might have established itself in their kidneys. To examine whether the virus might harm kidneys over time, Murray’s team then looked for indicators of long-term kidney disease, such as excess protein in the urine, in samples from 139 people, most of whom were infected with the 2003 strain of the virus. She reported2 in July that 40% of that group showed signs of long-term kidney disease.
However, Lyle Peterson, director of the division of vector-borne infectious diseases at the CDC, sees no cause for alarm given the current evidence. He points out that Murray’s latest study did not include a control group, and that a CDC study of some West Nile survivors in Colorado found no evidence of viral RNA in the subjects’ urine3.
Michael Busch, director of the Blood Systems Research Institute in San Francisco, California, told Nature that his team had also failed to find viral RNA, even though it had tested some of the same urine samples that Murray used. “Until multiple labs find the same results from the same blinded samples, everything must be taken with a grain of salt,” says Busch.
Murray maintains that there is an art to detecting RNA in urine. The single-stranded fragments are easily broken apart by enzymes in the fluid and by freezing and thawing when samples are shipped and stored. By contrast, samples that had travelled for just one hour from Murray’s lab to the University of Texas Medical Branch (UTMB) in Galveston for independent testing corroborated her findings1. Still, she says, she was shaken by the criticism. “I was starting to feel crazy. I wondered if I was committing career suicide.”
Murray has regained her confidence. In one electron micrograph image, not yet published, she points to a group of fuzzy spheres that look like West Nile virus in a cell found in the urine of a woman who suffered an infection in 2003. Other particles in urine can look like small, fuzzy balls, critics note. But Murray hopes that within a year she will have evidence that will silence the sceptics. With her new lab and a four-year grant from the National Institutes of Health, she plans to recruit 440 people — half of whom had West Nile — to a study to look for kidney disease. By next month she also plans to try to isolate and grow the virus from urine.
Murray says it’s not just a matter of defending her hypothesis, and others agree. “If we know this is a problem, we would know to monitor West Nile patients, and as soon as you saw some kidney enzymes acting abnormally, you could start to think about ways to prevent the progression of kidney disease,” says Frederick Murphy, a virologist at the UTMB.
No drugs have been shown to be effective against West Nile, for either the immediate infection or the long-term effects. “We need to start thinking about how to treat it,” Murray says. If her suspicions prove correct, that need will soon seem far more urgent than it did before.
Murray, K. et al. J. Infect. Dis. 201, 2–4 (2010).
Nolan, M. S. et al. PLoS ONE 7, e40374 (2012).
Gibney, K. B. et al. J. Infect. Dis. 203, 344–347 (2011).
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Maxmen, A. The hidden threat of West Nile virus. Nature 489, 349–350 (2012). https://doi.org/10.1038/489349a