coronavirusMiddle Eastern respiratory syndrome coronavirus (MERS-CoV), first identified in the fall of 2012 in a Saudi Arabian patient, has since infected over 180 individuals, causing 77 deaths. Antibodies to the virus and the viral genome have been found in dromedary camels in Jordan and Saudi Arabia, implicating those animals as the source of human infections. A new study reveals that the virus has infected camels throughout Saudi Arabia since at least 1992.

Serum, blood, and rectal and nasal swabs were collected from dromedary camels in November-December 2013 from southwestern, western, northwestern, eastern, and central regions of the Kingdom of Saudi Arabia. Of 203 serum samples, 150 (74%) were found to contain antibodies to MERS-CoV. The number of seropositive animals varied from 5% to 95% depending on location and the age of the animals (in general, seropositivity was higher in adult camels compared with young camels). Antibodies against MERS-CoV were also detected in archived serum samples from 1992 through 2010.

Polymerase chain reaction was used to detect viral nucleic acids in clinical specimens from camels. Viral nucleic acid was most frequently detected in nasal  swabs; only three rectal samples were positive. More samples from juvenile camels contained viral nucleic acids (36/104, 35%) than from adults (15/98, 15%). No viral nucleic acids were detected in the blood of these animals.

Phylogenetic analysis of approximately 3 kb of viral nucleic acid sequence revealed <1% divergence from published MERS-CoV sequences.

These findings indicate that dromedary camels are a reservoir of MERS-CoV. The finding of higher seroprevalence in older camels suggests that younger animals are infected as they are introduced into herds in which the virus is circulating. Proving that infected camels are the source of human infections will require epidemiological investigations of human cases where the infection might have been acquired from camels. If camels indeed spread the virus to humans, it will be important to determine the route. As not all MERS-CoV cases have documented exposure to camels, there should be other routes of infection other than contact with camels, such as through contaminated material or person to person contact.

MERS-CoV has been circulating in dromedary camels in Saudi Arabia since 1992, but it is likely that the virus has been infecting these animals even longer. Camels do not appear to be adversely affected by MERS-CoV infection, a situation often seen when host and pathogen have co-evolved for long periods of time. Whether or not this speculation is correct will require additional work.

I spoke with two of the authors of this new study, W. Ian Lipkin and Thomas Briese, on a special episode of the science show This Week in Virology. You can find TWiV special – MERS-coronavirus in dromedary camels at During this episode it was revealed that the investigators have propagated infectious MERS-coronavirus from nasal swabs of several dromedary camels.


On episode #273 of the science show This Week in Virology, the TWiVome dissect the finding that interferon lambda alleles predict the outcome of hepatitis C virus infection.

You can find TWiV #273 at

How to give a great lecture

21 February 2014

Virology class 2013There are many elements that go into making a great lecture, but the most important one is to lose the notes.

If you are giving lectures in a course at any level, the worst practice you can engage in is to rely on notes. This behavior is problematic for several reasons. You will not properly know the material, necessitating frequent glances at your notes. The students will notice this and consider you to be unengaged and not knowledgeable. Requiring notes will more or less tie you to the lectern, or to some kind of platform at the front of the room. If you carry the notes around the room as you talk you will be perceived as confused and not authoritative with respect to the subject. Get rid of the notes.

Not relying on notes will have huge benefits for your lectures. You will be able to speak conversationally instead of in a stilted manner necessitated by looking at an outline. You can move around the room. There is no better practice than to move away from the lectern directly in front of the students. You can look them in the eye as you speak, and engage them. They will feel that you have moved among them, rather than hiding behind the lectern. Let’s face it, the lectern is a crutch – it’s a good place to hide behind if you are nervous, and clutching the sides of the podium provides false confidence. Forget about all that. I use the lectern to hold my laptop and then stay away from it for the entire lecture.

When I lecture, I move along the front and sides of the classroom, looking at the students as I talk. I only look at each slide initially to receive my cue about what I will be saying. Do not to speak to the slide – it’s the audience you are interested in. Of course there might be times when you have to walk through a complicated pathway with your laser pointer. I always look at the class while I am pointing, rather than turning to the slide and forgetting the students.

Please do not complain that you cannot remember all of the material without relying on notes. You should either study the material until you know it by heart, or do not give the lecture at all. And do not make your slides a surrogate for notes. Even  worse than relying on notes is showing the class slides full of text and simply reading them. Keep the text to an absolute minimum. Use simple images and let them trigger what you have to say. You must know the material well enough to do this, otherwise you are wasting the students’ time.

It’s very important to focus on the audience; by doing so they will sense that you have a command of the material and that you are interested in teaching them. Look at them as you speak. An added benefit is that you will get many more questions this way than if you stand with your back to the audience and hide in the slides. And there is no better supplement to a great lecture than fielding questions from the audience.

There are many other elements to a great lecture, of course, such as proper delivery, having a genuine passion for the material, and arranging the elements to give a compelling story arc. No matter how hard you work on those elements, you lectures will suffer unless you lose the notes.


En esta sesión hablaremos acerca de virus que codifican por una enzima llamada transcriptasa reversa. Revisaremos los ciclos de replicación de los retrovirus y los hepadnavirus, y como éstos son capaces de copiar DNA a partir de RNA, incluyendo metodos tan barrocos como la iniciación y el intercambio de templados. Tambien incluiremos una discusión acerca de la integración de DNA y de retroelementos en nuestro genoma.


TWiV 272: Give peas a chance

16 February 2014

On episode #272 of the science show This Week in Virology, the TWiV team describes aphid control by using a viral capsid protein to deliver a spider toxin to plants, and a human endogenous retrovirus that enhances expression of a neuronal gene.

You can find TWiV #272 at

chicken market

To the collection of avian influenza viruses known to sporadically infect humans – H5N1, H7N9, H7N2, H7N3, H7N7, H9N2, and H10N7 – we can now add H10N8, recently found in two individuals in China.

Avian influenza virus H10N8 was first detected in tracheal aspirates from a 73 year old woman who was hospitalized in November 2013 for severe respiratory illness. The patient, who died, had previously visited a live poultry market. A second infection with this virus was detected in January 2014.

Virus isolated from tracheal aspirates on day 7 of illness was named A/Jiangxi-Donghu/346/2013(H10N8). Nucleotide sequence analysis of the viral genome reveals that it is a reassortant. The HA gene most closely resembles that of a virus isolated from a duck in Hunan in 2012, while the NA gene resembles that of a virus isolated from a mallard in Korea in 2010. All six other RNA segments resemble those from circulating H9N2 viruses in China. These viruses have also provided genes for H7N9 and H5N1 viruses.

Examination of the viral protein sequences provides some clues about virulence of the virus. The HA protein sequence reveals a single basic amino acid at the cleavage site, indicating that the virus is of low pathogenicity in poultry, like H7N9 virus. The sequence in the sialic acid binding pocket of the HA protein indicates a preference for alpha-2,3 linked sialic acids, typical  for avian influenza viruses (human influenza viruses prefer alpha-2,6 linked sialic acids). A lysine at amino acid 627 in the PB2 protein is known to enhance the ability of the virus to replicate at mammalian temperatures; the H10N8 virus has a mixture of lysine and glutamic acid, the residue associated with less efficient replication. The sequence of the M2 protein indicates that the virus is resistant to the antiviral adamantanes. In vitro testing indicated sensitivity to NA inhibitors Tamiflu and Relenza.

It is not known if this novel H10N8 virus will spread further in the human population. A novel influenza H7N9 virus was first detected in humans in early 2013 and has since caused 250 human infections with 70 deaths. Similar incursions of avian influenza viruses into humans have probably taken place for as long as humans have had contact with poultry. We are now adept at detecting viruses and therefore we are noticing these infections more frequently.

Live poultry markets are clearly a risk factor for humans to acquire infections with avian influenza viruses, as noted by Perez and Garcia-Sastre:

Live bird markets in Asia are undoubtedly the major contributor in the evolution of avian influenza viruses with zoonotic potential, a fact for which we seem to remain oblivious.

Given their role in transmitting new viruses from animals to humans, I wonder why live poultry markets are not permanently closed.


On episode #271 of the science show This Week in Virology, the TWiV crew discusses two reports on viruses that might have crossed kingdoms, from plants to honeybees and from plants to vertebrates.

You can find TWiV #271 at

EvolutionVirulence, the capacity to cause disease, varies markedly among viruses. Some viruses cause lethal disease while others do not. For example, nearly all humans infected with rabies virus develop a disease of the central nervous system which ultimately leads to death. In contrast, most humans are infected with circoviruses with no apparent consequence. Is there a benefit for a virus to be virulent?

One explanation for viral virulence is that it facilitates transmission. However, a comparison of infections caused by two enteric viruses, poliovirus and norovirus, does not support this general view. Both viruses infect the gastrointestinal tract and are spread efficiently among humans by fecal contamination. However, norovirus infection causes vomiting and diarrhea, while poliovirus infection of the intestine is without symptoms (the rare invasion of the nervous system, and subsequent paralysis, is an accidental dead end). Both viruses have successfully colonized humans for many years, so why does only one of them cause gastrointestinal tract disease?

Two recent studies of bacterial virulence provide some clues about the evolution of virulence. In one a commensal strain of Escherichia coli was serially propagated in the presence of macrophages, which are cells of the immune system that take up and destroy the bacteria. After many such passages, bacterial clones were isolated that escape phagocytosis and killing by macrophages. These clones had also acquired increased pathogenicity in mice. In other words, the genetic changes that allowed the bacteria to evade the immune response also lead to increased virulence.

In another example of evolution to virulence, it was found the the bacterium Pseudomonas aeruginosa can sense the presence of competing gram-positive bacteria because the latter shed the cell wall component peptidoglycan. In response to this molecule, P. aeruginosa secretes proteins that kill the other bacteria. These secreted proteins also make the bacterium more virulent in a host – in their absence, the bacteria are less virulent. In other words, P. aeruginosa damages its host in an attempt to remove nearby bacterial competitors.

In both bacterial examples, virulence can be viewed as collateral damage: the consequence of evading the immune response, or killing off competitors. Being virulent was not the primary goal. This explanation for bacterial virulence is straightforward and compelling: virulence is not directly selected for during evolution but comes along for the ride. Can it be applied to viruses?

All eukaryotic viruses must encode at least one protein that antagonizes host immune responses, otherwise they would be eliminated. These immune evasion proteins are certainly virulence factors: in general, when they are deleted or altered, the capacity of the virus to cause disease in a host is reduced. Like bacterial virulence, viral virulence might be collateral damage incurred by having to evade immune responses. This hypothesis is attractive but seems overly simplistic. If the ubiquitous and benign circoviruses did not evade host responses, then they would be eliminated from the human population.

The reasons why some viruses are virulent and others are not remain elusive. It is possible to reduce viral virulence by mutation, but this type of experiment does not reveal why viruses cause disease. The inverse experiment would be more informative: to select from a population of avirulent virus those that can cause disease. The results of such an experiment would help to identify the selection pressures that allow viruses to evolve to virulence.


TWiV 270: Homeland virology

2 February 2014

On episode #270 of the science show This Week in Virology, Vincent and Rich discuss avian influenza virus and an antiviral drug against smallpox with Dennis and Yoshi at the ASM Biodefense and Emerging Diseases Research Meeting in Washington, DC.

You can find TWiV #270 at

pig farmPorcine epidemic diarrhea arrived in the United States in the spring of 2013. The disease, caused by a coronavirus, was first identified in the United Kingdom in 1971, and has subsequently spread throughout Europe and Asia. The disease is a concern for the swine industry because it is associated with high case fatality ratios in suckling pigs.

Porcine epidemic diarrhea virus is a member of the coronavirus family, which also includes the SARS and MERS coronaviruses (CoV). Before 2013 the virus had not been isolated in North America. It was detected on a farm in Iowa in May and subsequently spread to 22 states. It is estimated that between 1-4 million pigs have died of the disease in the US.  Recently the virus was found on a Canadian pig farm in Middlesex County, where it most likely arrived from the US.

PEDV can infect pigs of all ages, but is most serious in nursing pigs in which the clinical symptoms are the most severe. The disease is characterized by acute vomiting and watery diarrhea which in nursing pigs leads to dehydration and frequently death. There is no treatment for the disease other than rehydration; no antiviral drugs are available, but a vaccine was developed in 2013. The virus does not infect humans.

Sequence analysis of genomes from three US isolates of PEDV indicate that they are most closely related to a virus isolated in 2012 in Anhui, China. These data suggest, but do not prove, that the US PEDV originated from China. How the virus might have arrived from that country is a matter of speculation. The virus is believed to move from farm to farm on trucks that are used to carry pigs, as well as on contaminated boots and clothing. Many farms observe strict biosecurity procedures in which trucks are properly washed, disinfected, and heated to inactivate the virus. However these procedures cost money and take time, and may be bypassed in some cases. If older pigs are asymptomatically infected, they might be transported to other farms and spread the virus. Once in a farm, stopping spread of the virus is difficult: it is spread by fecal-oral contamination.

The coronavirus family is divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus. Several human coronaviruses that cause common cold-like illness, as well as PEDV, are alphacoronaviruses. SARS-CoV and MERS-CoV are betacoronaviruses. Viruses in the alphacoronavirus and betacoronavirus genera are believed to have originated from bats, while birds might have been the origin of viruses in the other two genera. Analysis of the PEDV genome sequence indicate that the 5’-untranslated region is similar to that of a bat coronavirus. Based on this information it has been suggested that PEDV originated from a cross-species transfer of a bat alphacoronavirus into pigs.

National Hog Farmer is not usually on my reading list, but it has a good summary of porcine epidemic diarrhea.