TWiV 298: MV-NIS de myelo

On episode #298 of the science show This Week in Virology, the TWiV gang answers follow-up questions about the Ebola virus outbreak in West Africa, then discuss treatment of  disseminated multiple myeloma with oncolytic measles virus.

You can find TWiV #298 at

TWiV 297: Ebola! Don’t panic

On episode #297 of the science show This Week in Virology, the TWiVites present an all-ebolavirus episode, tackling virology, epidemiology, and approaches to prevention and cure that are in the pipeline.

You can find TWiV #297 at

Is it Ebolavirus or Ebola virus?

Filovirus virionWhen I drafted my article for TakePart (Don’t Panic – Ebola Isn’t Heading For You), I used the term ‘ebolavirus’ throughout, but the editors changed every instance to ‘Ebola virus’. Understanding which term is correct is far more complicated than you might imagine.

A new virus was first isolated in 1976 from patients during an outbreak of hemorrhagic fever in southern Sudan and northern Zaire. The name Ebola virus was proposed to describe the agent of this outbreak:

…the name Ebola virus is proposed for this new agent. Ebola is a small river in Zaire which flows westward, north of Yambuku, the village of origin of the patient from whom the first isolate was obtained.

The name was further modified with the subsequent finding of distinct isolates of the virus (e.g. Zaire Ebola virus, Sudan Ebola virus, Reston Ebola virus). In 2002 the virus names were contracted (Zaire ebolavirus, Sudan ebolavirus).

The way that viruses are named is regulated by the International Committee on Taxonomy of Viruses (ICTV). The current virus nomenclature for the Ebolaviruses is as follows:

Family: Filoviridae
Genus: Ebolavirus
Species (5)Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, Zaire ebolavirus

This is why I used ebolavirus in the original draft of my article.

However, this new nomenclature did not work well, as summarized in a 2010 article, Proposal for a revised taxonomy of the family Filoviridae:

Five to eight years have passed since the introduction of the names Cote d’Ivoire ebolavirus [sic], Reston ebolavirus, Sudan ebolavirus, and Zaire ebolavirus for the members of the four recognized ebolavirus species. Instead of using these names, the overwhelming majority of publications refer to “Ebola virus” instead of Zaire ebolavirus, a preference that is also followed by the public press.

The authors conclude that introducing the name ‘Zaire ebolavirus’ was an error, and recommend reverting to the traditional virus name, Ebola virus:

Retrospectively, the virus nomenclature in most published articles will then be correct. Likewise, press articles, which almost invariably refer to “Ebola virus,” and usually with that term aim at referring to the virus that is currently officially named “Zaire ebolavirus,” will be correct retrospectively and prospectively. As the traditional names are different from the species names, confusing species and virus names will be much more difficult, even in the absence of taxonomic education.

When this proposal is officially ratified by the ICTV the nomenclature will be as follows:

Family: Filoviridae
Genus: Ebolavirus
Species: Tai Forest ebolavirus
Virus: Tai Forest virus (formerly Cote d’Ivoire ebolavirus)
Species: Reston ebolavirus
Virus: Reston virus
Species: Sudan ebolavirus
Virus: Sudan virus
Species: Zaire ebolavirus
Virus: Ebola virus
Species: Bundibugyo ebolavirus
Virus: Bundibugyo virus

This discussion leads us to the important difference between a virus and a species.  A virus species is defined as a polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche. According to the ICTV rules of nomenclature, virus species names are italicized with the first letter of the name capitalized (Zaire ebolavirus). Virus names (poliovirus) are written in lower case (except if a part of the virus name is a proper noun, e.g. Coxsackievirus) in non-italicized script.

The editors at TakePart changed my ‘ebolavirus’ to Ebola virus because that is the term they are familiar with. Using this name is not correct because Sudan virus, not Ebola virus, is responsible for the current outbreak in Uganda.

Incidentally, the virus I work on, poliovirus, is a member of the family Picornaviridae, genus Enterovirus, species Human enterovirus C. Poliovirus is the name of the virus. But you will often find it incorrectly called ‘polio virus’ in the popular press. At one time this virus was called ‘poliomyelitis virus’ which was shortened to ‘poliovirus’, not ‘polio virus’.

How lethal is ebolavirus?

Ebola seropositivity GabonAfter we discussed newly discovered entry factors for ebolavirus and hepatitis C virus on TWiV 166, the New York Times covered part of the story in Key protein may give Ebola virus its opening. Given my recent interest in the case fatality ratio of avian influenza H5N1, I was intrigued by the following introductory statement:

Of the pathogens that keep worried scientists awake at night, few rival Ebola for ruthless efficiency. The virus contains just seven genes, yet it manages to kill up to 90 percent of the people it infects.

Is it true that the fatality rate of ebolavirus is ‘up to 90 percent’? According to the WHO page on Ebola haemorrhagic fever,

Zaïre, Sudan and Bundibugyo species have been associated with large Ebola haemorrhagic fever (EHF) outbreaks in Africa with high case fatality ratio (25–90%) while Côte d’Ivoire and Reston have not. Reston species can infect humans but no serious illness or death in humans have been reported to date.

There have been roughly 1850 recorded cases with over 1200 deaths since ebolavirus was discovered, an average fatality rate of 65%. But have there been only 1850 human infections?

The answer is clearly no. The results of several serological surveys have shown that many individuals have antibodies against Zaire ebolavirus – purportedly the most lethal. The results of one study revealed antibodies in 10% of individuals in non epidemic regions of Africa. A similar seroprevalence rate (9.5%) was reported in villages near Kikwit, DRC where an outbreak occurred in 1995. In addition, a 13.2% seroprevalence was detected in the Aka Pygmy population of Central African Republic. No Ebola hemorrhagic fever cases were reported in these areas.

A more recent study examined sera from 4,349 individuals in 220 villages in Gabon. Antibodies against Zaire ebolavirus were detected in 15.3% of those tested, with the highest levels in forested regions (see map). The authors believe that the seropositive individuals had mild or asymptomatic ebolavirus infection:

The high frequency of ‘immune’ individuals with no disease or outbreak history raises questions as to the real pathogenicity of ZEBOV for humans in ‘natural’ conditions.

These findings indicate that the fatality rates of Zaire ebolavirus that are quoted widely are likely to be vast overestimates. Why the infection is more lethal during outbreak conditions is not known. One possibility is related to the size of the viral inoculum received. During outbreaks the virus is spread by contact with the blood, secretions, organs or other body fluids of infected individuals, which contain very large quantities of virus. In contrast, infections in nature – by contact with contaminated fruit, for example – may involve far less virus.

Whether we are discussing avian H5N1 influenza, ebolavirus, or even the fictitious MEV-1, do not assume that widely quoted fatality rates are correct – check the scientific literature!


Should we fear avian H5N1 influenza?

Becquart P, Wauquier N, Mahlakõiv T, Nkoghe D, Padilla C, Souris M, Ollomo B, Gonzalez JP, De Lamballerie X, Kazanji M, & Leroy EM (2010). High prevalence of both humoral and cellular immunity to Zaire ebolavirus among rural populations in Gabon. PloS one, 5 (2) PMID: 20161740

TWiV 89: Where do viruses vacation?

Hosts: Vincent Racaniello and Alan Dove

On episode #89 of the podcast This Week in Virology, Vincent and Alan review recent findings on the association of the retrovirus XMRV with ME/CFS, reassortment of 2009 pandemic H1N1 influenza virus in swine, and where influenza viruses travel in the off-season.

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TWiV 83: An hour with Dr. Kiki

Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Kirsten Sanford

On episode #83 of the podcast This Week in Virology, Vincent, Alan, Rich, and special guest Dr. Kirsten Sanford talk about her career in science media, then consider whether smallpox eradication led to the AIDS pandemic, high fidelity RNA synthesis, and a new Ebola virus vaccine.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $75-$500 off a Drobo.

Win a free Drobo S! Contest rules here.

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Virology lecture #23: Emerging viruses

Download: .wmv (346 MB) | .mp4 (91 MB)

Visit the virology W3310 home page for a complete list of course resources.

Contagion, the movie

Contagion (2001)Contagion is the name of a new action-thriller movie about a global outbreak of a deadly viral disease. Slated to be released in 2011, it is directed by Steven Soderbergh and stars Matt Damon, Kate Winslet, Jude Law, Marion Cotillard, Gwyneth Paltrow, and Lawrence Fishburne. That’s certainly an outstanding crew, but will they get the science right?

According to Beyond Hollywood, “the film will have most of the big names playing doctors who are called to duty by the Centers for Disease Control when a major viral outbreak starts killing people around the world. The cast will then be split up and jet off to different continents.” Dread Central calls it ‘the deadly viral outbreak film of the decade’. Apparently Jude Law will play “a kind of unbridled blogger who’s a sort of scaremonger. Basically, it’s about a deadly virus unleashed and you see it from many different points of view, whether it be the public, medical care, politicians.”

The particular virus involved in Contagion has not been identified, but I have a good source which tells me that it’s a paramyxovirus. That’s not too hard to believe since the lethal Hendra and Nipah viruses are both members of the same family.

We’ll have to wait for more information to determine if the science in the film is credible. I do know that a prominent virologist, for whom I have a great deal of respect, has been hired as a script consultant. Whether or not the director and writer actually listen to that virologist is another question.

Moviegoers may know about the eponymous 2001 sci-fi movie (pictured) in which a group of terrorists concocted a seemingly unstoppable strain of Ebola. The first target is the President of the United States. Scientific reality just isn’t exciting enough for the movies.

An antiviral for enveloped viruses

LJ001Broad spectrum antibiotics are available that act against a wide range of bacteria, including both gram-positive and gram-negative species. In contrast, our antiviral arsenal is exceedingly specific. Nearly all the known antivirals block infection with one or two different viruses. The discovery of a compound that blocks infection with many different enveloped viruses may change the landscape of antiviral therapy.

A small molecule has been discovered that inhibits infection by a wide range of viruses with membranes, the so-called enveloped viruses. The compound, called LJ001, is a derivative of aryl methylene rhodanine. It was discovered in a search for compounds that block the entry of Nipah virus into cells. LJ001 was then found to block infection of cells by a wide variety of enveloped viruses, including filoviruses (Ebola, Marburg); influenza A virus; arenaviruses (Junin), bunyaviruses (Rift Valley fever virus, LaCrosse virus); flaviviruses (Omsk hemorrhagic fever virus, Russian spring-summer encephalitis virus, yellow fever virus, hepatitis C virus, West Nile virus); paramyxoviruses (Nipah virus, parainfluenza virus, Newcastle disease virus); retroviruses (HIV-1, murine leukemia virus); rhabdoviruses (vesicular stomatitis virus); and poxviruses (cowpox virus, vaccinia virus). The compound had no effect on viruses without an membrane, such as adenovirus, coxsackievirus, and reovirus.

To determine which step of viral infection is blocked, LJ001 was added at different times during infection. Inhibition of infection was observed when LJ001 and virus were incubated before being added to the cell. However, if the virus was allowed to enter the cell, addition of the compound had no effect on the production of infectious virus. Inclusion of LJ001 into the culture medium did prevent virus spread to neighboring cells.

LJ001 inhibits such a wide spectrum of viruses because it targets a feature common to all of them: the viral envelope (see image of influenza virus for an example). The compound blocks virus infection by inserting into the viral membrane and inhibiting entry into the cell. It does not block virus attachment to cells, but impairs fusion of the viral and cell membranes, a step essential for entry of the viral genome into cells. However, LJ001 is not toxic to cells, and does not inhibit the fusion of neighboring cells caused by some viral infections.

How might LJ001 impair viral but not cellular membranes? One explanation is that the compound damages both viral and cell membranes. The latter can be repaired and consequently escape the toxic effects of the drug. In contrast, viral membranes are static, and once damaged by LJ001 they can no longer function properly during virus entry into cells.

Whether LJ001 and derivatives will be useful for treating virus infections in animals awaits the results of testing in animal models and then in humans. Meanwhile, an interesting question is whether viral mutants resistant to LJ001 and its derivatives will emerge. Just because the drug targets a component derived from the host cell does not mean that resistance will not emerge. The drug brefeldin A, an inhibitor of poliovirus, blocks a cellular enzyme, yet viral mutants resistant to the drug have been identified. One possibility for the mechanism of resistance could be amino acid changes in viral glycoproteins that protect the viral membrane from damage caused by LJ001.

Perhaps it’s not a matter of whether mutants resistant to LJ001 will emerge, but when they will be identified.

Wolf, M., Freiberg, A., Zhang, T., Akyol-Ataman, Z., Grock, A., Hong, P., Li, J., Watson, N., Fang, A., Aguilar, H., Porotto, M., Honko, A., Damoiseaux, R., Miller, J., Woodson, S., Chantasirivisal, S., Fontanes, V., Negrete, O., Krogstad, P., Dasgupta, A., Moscona, A., Hensley, L., Whelan, S., Faull, K., Holbrook, M., Jung, M., & Lee, B. (2010). A broad-spectrum antiviral targeting entry of enveloped viruses Proceedings of the National Academy of Sciences, 107 (7), 3157-3162 DOI: 10.1073/pnas.0909587107

TWiV 47: Vertical vaccine farm

twiv-200Hosts: Vincent Racaniello and Dick Despommier

On episode #47 of the podcast “This Week in Virology”, Vincent and Dick discuss influenza virus-like particle vaccines produced in insect and plant cells, rapid sharing of influenza research, and answer listener questions about cytomegalovirus, viral evolution and symbiosis and much more.

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Links for this episode:
A Farm on Every Floor
Influenza virus-like particles in insect and plant cells
PLoS Currents: Influenza
Transmission of 2009 H1N1 influenza virus to turkeys [Thanks Debbie!]
Baxter produces Vero cell H1N1 vaccine [Thanks Peter!]
Boundaries of Darwinism podcast [Thanks David!]
Phages in human intestine: papers onetwothree [Thanks Terry!]
Post-exposure varicella vaccine [Thanks Patricia!]
Open science movement hereherehere, and here [Thanks Jim!]
Graduate programs in virology [Thanks Greggory and Blake!]
Post-exposure Marburg and Ebola vaccines [Thanks John!]
Vaccinia infection in the laboratory [Thanks Russ!]
Animations of bacteriophage T4 life cycle [Thanks Jim!]

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