TWiV 411: Chicken runs

The TWiVeroos examine a reverse spillover of Newcastle disease virus vaccines into wild birds, and identification of a protein cell receptor for murine noroviruses.

You can find TWiV #411 at, or listen below.

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Measles in the brain: Fusion gone awry

paramyxovirus fusionThe entry of enveloped viruses into cells begins when the membrane that surrounds these virus particles fuse with a cell membrane. The process of virus-cell fusion must be tightly regulated, to make sure it happens in the right cells. The fusion activity of measles viruses isolated from the brains of AIDS patients is not properly regulated, which might explain why these viruses cause disease in the central nervous system.

Measles virus particles bind to cell surface receptors via the viral glycoprotein HN (illustrated). Once the viral and cell membranes have been brought together by this receptor-ligand interaction, fusion is induced by a second viral glycoprotein called F, and the viral RNA is released into the cell cytoplasm. The N-terminal 20 amino acids of F protein are highly hydrophobic and form a region called the fusion peptide that inserts into target membranes to initiate fusion. Because F-protein-mediated fusion can occur at neutral pH, it must be controlled, to ensure that virus particles fuse with only the appropriate cell, and to prevent aggregation of newly made virions. The fusion peptide of F is normally hidden, and conformational changes in the protein thrust the it toward the cell membrane (illustrated). These conformational changes in the F protein, which expose the fusion peptide, are thought to occur upon binding of HN protein to its cellular receptor.

During a recent outbreak of measles in South Africa, several AIDS patients died when measles virus entered and replicated in their central nervous systems. Measles virus normally enters via the respiratory route, establishes a viremia (and the characteristic rash) and is cleared within two weeks. The virus is known to enter the brain in up to half of infected patients, but without serious sequelae. The measles inclusion body encephalitis observed in these AIDS patients typically occurs in immunosuppressed individuals several months after infection with measles virus.

Measles virus isolated postmortem from these two individuals had a single amino acid change in the F glycoprotein, from leucine to tryptophan at position 454. This single amino acid change allowed viruses to fuse with cell membranes without having to first bind a cellular receptor via the HN glycoprotein. In other words, the normal mechanism for regulating measles virus fusion – binding a cell receptor – was bypassed in these viruses. This unusual property might have allowed measles virus to spread throughout the central nervous system, causing lethal disease.

How did these mutant viruses arise in the AIDS patients? Because these individuals had impaired immunity as a result of HIV-1 infection, they were not able to clear the virus in the usual two weeks. As a consequence, the virus replicated for several months. During this time, the mutation might have arisen that allowed unregulated fusion of virus and cell, leading to unchecked replication in the brain. Alternatively, the mutation might have been present in virus that infected these individuals, and was selected in the central nervous system.

An interesting question is whether these neurotropic measles viruses can be transmitted by aerosol between hosts – a rather unsettling scenario. Fortunately, we do have a measles virus vaccine that effectively prevents infection, even with these mutant viruses.

TWiV 311: Bulldogs go viral

On episode #311 of the science show This Week in Virology, Vincent visits the University of Georgia where he speaks with Zhen Fu and Biao He about their work on rabies virus and paramyxoviruses.

You can find TWiV #311, audio and video versions, at

TWiV 243: Live from ASV at Penn State

On this episode of the science show This Week in Virology, which was recorded before a large enthusiastic audience at the annual meeting of the American Society for Virology, Vincent, Rich, and Kathy speak with Rebecca and Christiane about their work on metapneumoviruses and noroviruses.

You can find TWiV #243 at

TWiV 185: Dead parrots and live Wildcats

On episode #185 of the science show This Week in Virology, Vincent visits with members of the Department of Microbiology and Immunology at Northwestern University School of Medicine to discuss their work on herpesviruses and parainfluenzaviruses.

You can find TWiV #185 at

TWiV 183: Bats out of hell

On episode #183 of the science show This Week in Virology, Connor Bamford joins the TWiV team to discuss bats as hosts for major mammalian paramyxoviruses.

You can find TWiV #183 at

TWiV 144: HIV gets the (zinc) finger

zinc finger nucleaseHosts: Vincent Racaniello, Rich Condit, and Alan Dove

Vincent, Rich, and Alan discuss live blogging of scientific meetings, the current outbreak of Hendra virus is Australia, and using zinc finger nucleases to make HIV-resistant CD4 cells.

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Vaccine adverse events: Causal or coincidental? (Lancet)
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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.

Reverse zoonoses: Human viruses that infect other animals

bonoboThe many human viral diseases that have crossed from other animal species  – such as AIDS, Ebola, SARS, encephalitis and respiratory diesease caused by henipaviruses – demonstrate the pathogenic potential of the zoonotic pool. Are there also reverse zoonoses – diseases of humans that are transferred to other animal species?

An example of a reverse zoonosis occurred just last week at Lincoln Park Zoo in Chicago, where a 9 year old chimpanzee died of respiratory disease caused by human metapneumovirus. This member of the paramyxovirus family is responsible for approximately 10% of all respiratory tract infections. All seven members of a group of chimpanzees were infected with the virus, but only one became ill. The virus was likely transmitted to the chimps by humans, but precisely how and when is not known. Outbreaks of fatal respiratory disease in wild chimpanzees have been reported previously, and human metapneumovirus has been one of several human viruses isolated from these primates. Such infections are expected to occur more frequently in zoological parks, and ando also in game preserves as human encroachment of these facilities increases.

Influenza virus may also be frequently transmitted from humans to other animal species. An outbreak of influenza recently lead to the death of 6 bonobos (a species of chimpanzee) in a Congo wildlife sanctuary. Although the influenza subtype responsible for the outbreak has not been identified, it has been suggested that the source was one or more visitors during the February epidemic of influenza in Kinshasha.

Human influenza viruses are frequently isolated from pigs. Since its emergence in 1968, the H3N2 subtype has infected pigs many times throughout the world, and has often caused serious outbreaks. More recently the influenza H1N1 subtype has been shown to infect pigs. Influenza viruses remain in the pig population for long periods of time, and may serve as reservoirs for the recycling of older influenza virus strains back into the human population.

Just as increasing human population, travel, and the global food business increase the likelhood that viruses will jump from animals into humans, the same factors ensure the reverse spread as well – often with dire consequences for zoological parks and wild and domestic animals. And the viruses we pass on may come back to haunt us another day.

Kaur, T., Singh, J., Tong, S., Humphrey, C., Clevenger, D., Tan, W., Szekely, B., Wang, Y., Li, Y., Alex Muse, E., Kiyono, M., Hanamura, S., Inoue, E., Nakamura, M., Huffman, M., Jiang, B., & Nishida, T. (2008). Descriptive epidemiology of fatal respiratory outbreaks and detection of a human‐related metapneumovirus in wild chimpanzees at Mahale Mountains National Park, Western Tanzania. American Journal of Primatology, 70 (8), 755-765 DOI: 10.1002/ajp.20565

Yu, H., Zhou, Y., Li, G., Zhang, G., Liu, H., Yan, L., Liao, M., & Tong, G. (2009). Further evidence for infection of pigs with human-like H1N1 influenza viruses in China Virus Research, 140 (1-2), 85-90 DOI: 10.1016/j.virusres.2008.11.008

de Jong, J., Smith, D., Lapedes, A., Donatelli, I., Campitelli, L., Barigazzi, G., Van Reeth, K., Jones, T., Rimmelzwaan, G., Osterhaus, A., & Fouchier, R. (2007). Antigenic and Genetic Evolution of Swine Influenza A (H3N2) Viruses in Europe Journal of Virology, 81 (8), 4315-4322 DOI: 10.1128/JVI.02458-06