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About viruses and viral disease
On episode #293 of the science show This Week in Virology, Vincent visits Melbourne, Australia and speaks with Melissa, Alex, Gilda, and Paul about their work on HIV infection of the central nervous system, West Nile virus, microbicides for HIV, and the Koala retrovirus.
You can find TWiV #293 at www.microbe.tv/twiv.
This discussion of West Nile virus was recorded at the headquarters of the American Society for Microbiology during a “Microbes After Hours” event on May 6, 2013. The speakers are Dr. Lyle Petersen Lyle R. Petersen, M.D., M.P.H., director of the Division of Vector-Borne Diseases at CDC, and Dr. Roberta DeBiasi, MD, FIDSA, Associate Professor of Pediatrics at George Washington University School of Medicine, Acting Chief and Attending Physician in the Division of Pediatric Infectious Diseases at Children’s National Medical Center, and investigator at Children’s Research Institute in the Center for Translational Science in Washington, D.C.
MWV Episode 70 – Microbes After Hours – West Nile Virus from microbeworld on Vimeo.
Hosts: Vincent Racaniello, Dickson Despommier, Rich Condit, and Alan Dove
The complete TWiVome deconstructs the movie Contagion.
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Dickson – Guinea Pig Doctors by Jon Franklin
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A type of human encephalitis – an infection of the brain – has been known to affect the indigenous people living in the Sakha Republic of Russia since the mid-1800s. The available clinical and epidemiological evidence suggests that the disease is caused by a pathogen, but proving this has been difficult.
The disease is called Vilyuisk encephalitis (VE) due to its prevalence in the Vilyui River Valley. After an outbreak of VE in the 1950s, when 1% of the local population was affected, clinical aspects of the disease were carefully documented by the Russian health ministry. VE is a progressive neurological disorder with acute, subacute, and chronic presentations. Acute disease begins with fever, chills, headache, vomiting and rapid progression to confusion, quadraparesis and death within a few months, with 15% mortality. Subactue VE begins in a similar manner, followed by remission, and then the return of neurological symptoms including spastic paralysis and dementia. The mean duration of illness of 3.5 years. Chronic VE is a long-term form of subacute VE with no acute phase.
It is not known how VE is transmitted among the indigenous Sakha. Most live in wooden huts with no sanitary facilities; running water is available only after the spring thaw (May – August) when the snows melt. Why the onset of VE coincides with the subsequent increase in outdoor activities such as fishing, hunting, and herding cattle, is not understood.
The Sakha Republic is located north of the trans-Siberian railway and several degrees south of the Arctic circle. It is a harsh environment where winter temperatures are −40 degrees F, and there are no roads or railways allowing travel to the rest of Russia. These conditions may in part explain why the disease has not spread extensively. In the 1980s the disease moved south as the indigenous people migrated towards the regional capital of Yakutsk, where VE had never been observed.
Attempts to identify a viral etiology of VE were carried out in Moscow in 1954-57 by inoculating blood, stool, nasopharyngeal, cerebrospinal fluid and brain samples from VE patients into mice. Eleven virus isolates were obtained, and one, now called Vilyuisk human encephalitis virus (VHEV), which originated from CSF, has been the most studied. Sequence analyses have revealed that VHEV is related to Theiler’s murine encephalomyelitis virus (TMEV), a member of the picornavirus family that also includes poliovirus. TMEV is a natural pathogen of mice, in which it causes a persistent infection of the central nervous system. This property of TMEV was consistent with the pathogenesis of VE in humans. However, VHEV has not been identified in any other patient with VE, and may be a laboratory contaminant that originated from the mice used to isolate the virus.
More recently, Theiler-like viruses have been isolated from humans. The first, called Saffold virus (SAFV), was isolated in 1981 from an 8 month old infant with fever of undetermined origin. The second was isolated 25 years later from the nasopharynx of a 23 month old infant. Subsequent epidemiological studies have revealed that SAFV-like viruses are ubiquitous human viruses that infect during early childhood. These findings suggest that VHEV is a human virus, and not a laboratory contaminant. Whether VHEV causes Vilyuisk encephalitis remains to be determined.
There has been little progress in research on VE, mainly as a consequence of the remote location of the Sakha Republic, and the decline in resources for VE surveillance. If these obstacles could be overcome, here are some of the important questions about the disease that should be answered:
Some of these questions are being addressed by neurologist Howard L. Lipton in work supported by the US National Institutes of Health.
Zoll J, Erkens Hulshof S, Lanke K, Verduyn Lunel F, Melchers WJ, Schoondermark-van de Ven E, Roivainen M, Galama JM, & van Kuppeveld FJ (2009). Saffold virus, a human Theiler’s-like cardiovirus, is ubiquitous and causes infection early in life. PLoS pathogens, 5 (5) PMID: 19412527
Pritchard, A. (1992). Nucleotide sequence identifies vilyuisk virus as a divergent Theiler’s virus Virology, 191 (1), 469-472 DOI: 10.1016/0042-6822(92)90212-8
In an NYTimes Op-Ed article called “The Scary Caterpillar”, Jeffrey Lockwood wrote about potential use of a virus as a weapon of bioterrorism:
What if a terrorist group announced that their operatives had introduced Rift Valley fever into the United States? This mosquito-borne disease would make West Nile virus look like a case of the sniffles. Given that virtually every corner of America has a native species of mosquito capable of transmitting the virus, Rift Valley fever could spread across the nation. Hundreds of thousands of people could be sickened, with thousands dying and many more falling blind. The livestock industry could lose billions of dollars as animals aborted their fetuses and succumbed to bloody diarrhea. Imagine the fear if every mosquito bite this summer could be the precursor of a disease that would cause your brain to become inflamed or your internal organs to hemorrhage?
To me it reads like a movie script, not a serious assessment. Let’s dissect the statement and find out the truth.
Rift Valley fever virus (RVFV) is a member of the Bunyaviridae, a large family of enveloped, RNA containing viruses that includes the well known hantaviruses. The virus was first isolated in 1930 from a lamb during investigation of a disease that was causing abortion and mortality in Kenyan sheep. Since then the virus has caused large outbreaks of disease in livestock. Because infection may lead to high rates of abortion and death, the virus has substantial economic impact. The virus is transmitted among livestock by mosquito vectors. Epizootics often occur when precipitation is high, favoring mosquito breeding.
Outbreaks were confined to livestock in Africa until September 2000 when the disease was observed in Saudi Arabia and Yemen. These epidemics were believed to be a consequence of more abundant mosquito populations that resulted from heavy rain and flooding near the Asir mountains. There is some concern that the virus might spread to Europe, but that has not been observed.
RVFV may also infect humans; in the vast majority of such cases, transmission occurs by direct contact with the blood or organs of infected animals. Some infections are transmitted by mosquitoes, but this is certainly not the main route of human infection.
How serious is human disease caused by RVFV? Most cases are mild, and involve non-specific symptoms including fever, muscle and joint pain, and headache; neck stiffness and vomiting may also occur. About 1% of infected patients may develop more serious disease including eye infection, meningoencephalitis, and hemorrhagic fever. Fatality is typically less than 1%, although in the outbreak in Yemen and Saudi Arabia it was 12%.
What mosquitoes are known to carry RVFV? The principal vector appears to be mosquitoes of the Aedes genus, although Culex species have been shown to transmit the virus in the laboratory. However, the particular species known to transmit RVFV in Africa are not the predominant type of mosquito in the US.
It is clear that nearly every statement in the paragraph reproduced above from “The Scary Caterpillar” is an exaggeration. Rift Valley disease usually does not make West Nile encephalitis look like a case of the sniffles; every corner of America does not have a mosquito capable of transmitting the virus, and the disease severity is overstated. Whether or not the virus could be entrenched in the US is not known – we might not have the proper climate for the levels of mosquito infestation that is required for transmission. Like all viruses, RVFV is capable of changing so that it could cause extensive human disease in the US – but our current understanding of the viral disease is completely inconsistent with Lockwood’s description.
There are other bothersome errors in the passage. The writer calls Rift Valley Fever a ‘mosquito borne disease’, but readers of virology blog know that it is the virus that is borne by the mosquito, not the disease. And the terrorists would not be introducing the disease into the US – they would introduce the virus. Finally, the sentence “This mosquito-borne disease would make West Nile virus look like a case of the sniffles” just isn’t right – you can’t compare a disease with a virus. But these are small errors when compared with the outright exaggerations of the article.
Perhaps the fact that the author of the Times piece, Jeffrey A. Lockwood, is not a virologist, but a professor of natural sciences and humanities at the University of Wyoming, explains why he does not understand the biology of Rift Valley fever virus.
Moutailler, S., Krida, G., Schaffner, F., Vazeille, M., & Failloux, A. (2008). Potential Vectors of Rift Valley Fever Virus in the Mediterranean Region Vector-Borne and Zoonotic Diseases, 8 (6), 749-754 DOI: 10.1089/vbz.2008.0009
Turell, M., Dohm, D., Mores, C., Terracina, L., Wallette, D., Hribar, L., Pecor, J., & Blow, J. (2008). Potential for North American Mosquitoes to Transmit Rift Valley Fever Virus Journal of the American Mosquito Control Association, 24 (4), 502-507 DOI: 10.2987/08-5791.1