virology blog
About viruses and viral disease
On episode #289 of the science show This Week in Virology, Vinny and the capsids answer listener questions about the definition of life, state vaccination laws, the basic science funding problem, viral ecology, inactivation of viruses by pressure, and much more.
You can find TWiV #289 at www.microbe.tv/twiv.
The SARS pandemic of 2002-2003 is believed to have been caused by a bat coronavirus (CoV) that first infected a civet and then was passed on to humans. The isolation of a new SARS-like coronavirus from bats suggests that the virus could have directly infected humans.
A single colony of horseshoe bats (Rhinolophus sinicus) in Kunming, Yunnan Province, China, was sampled for CoV sequences over a one year period. Of a total of 117 anal swabs or fecal samples collected, 27 (23%) were positive for CoV sequences by polymerase chain reaction (PCR). Seven different SARS-like CoV sequences were identified, including two new ones. For the latter the complete genome sequence was determined, which showed a higher nucleotide sequence identity (95%) with SARS-CoV than had been previously observed before among bat viruses.
One of these new viruses was recovered by infecting monkey cell cultures with one of the PCR-positive samples. This virus could infect human cells and could utilize human angiotensin converting enzyme 2 (ACE2) as an entry receptor. The infectivity of this virus could also be neutralized with sera collected from seven different SARS patients.
None of the SARS-like coronaviruses previously isolated from bats are able to infect human cells. The reason for this block in replication is that the spike glycoprotein of these bat viruses do not recognize ACE2, the cell receptor for SARS-CoV. SARs-like CoVs isolated from palm civets during the 2002-2003 outbreak have amino acid changes in the viral spike glycoprotein that improve its interaction with ACE2. The civet was therefore believed to be an intermediate host for adaptation of SARS-CoV to humans. The isolation of bat SARS-like CoVs that can bind human ACE2 and replicate in human cells suggests that the virus might have spread directly from bats to humans.
This finding has implications for public health: if SARS-like CoVs that can infect human cells are currently circulating in bats, they have the potential to infect humans and cause another outbreak of disease. The authors believe that the diversity of bat CoVs is higher than we previously knew:
It would therefore not be surprising if further surveillance reveals a broad diversity of bat SL-CoVs that are able to use ACE2, some of which may have even closer homology to SARS-CoV than SL-CoV-WIV1.
Is there any implication of this work for the recently emerged MERS-CoV? Sequences related to MERS-CoV have been found in bats, and given that bats are known to be hosts of a number of viruses that infect humans, it is reasonable to postulate that MERS-CoV originated in bats. So far a 190 fragment of MERS-CoV nucleic acid has been found in a single bat from Saudi Arabia. Identification of the reservoir of MERS-CoV will require duplicating the methods reported in this paper: finding the complete viral genome, and infectious virus, in bats.
In my recent keynote address to the Brazilian Virology Society entitled The World of Viruses, I presented my list of ten seminal virologists. The idea to include such a discussion came from David Baltimore, who sent me the following note:
Since you have been thinking about the history of virology, I thought I would share a list with you. Someone asked me to list the 10 most important virologists in history. I came up with 12. But I wondered if you had to make such a list, who you would include.
David Baltimore’s list included the following individuals:
Obviously such lists are very personal and will certainly differ (although there would likely be names in common). Here is the list of ten seminal virologists:
I sent my list to David, who replied:
I suppose this is a discussion that could go on endlessly but I find Doherty a very odd choice (more an immunologist than virologist) and Hershey a surprising choice, although he makes sense for having shown that the guts of a virus is its nucleic acid. And I miss Rous and Stanley very much. When Stanley crystallized TMV he brought together chemistry and virology, made life a continuum from the inorganic and put viruses at the cusp. Then Hershey makes sense because he got inside the virus and found the key chemical. Rous, you might argue, did more for cancer research than for virus research but I still think that the link of viruses to cancer changed the trajectory of virus research.
Interesting discussion.
Rich Condit and Alan Dove also have their own lists of ten virologists, which we’ll share on an upcoming TWiV. Making such lists stimulates valuable discussion about discoveries that set the future course of virology. It’s very much like the discussion about whether or not viruses are alive – the answer is not as important as the thoughts involved in getting there.
Who would be on your list of ten seminal virologists?
Hosts: Vincent Racaniello and Dickson DespommierOn episode 20 of the podcast This Week in Parasitism, Vincent and Dickson continue their discussion of nematodes with the whipworm Trichuris trichiura.
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A number of readers have asked when we would have information about the safety of the influenza 2009 H1N1 vaccine. The World Health Organization has just released briefing note #16 “Safety of pandemic vaccines” in which they summarize vaccination information from 16 countries in which 80 million doses of vaccine have been administered.
Side effects commonly reported include swelling, redness, or pain at the injection site, which usually resolve soon after vaccination. Fever, headache, fatigue, muscle aches, and a variety of allergic reactions, occurring shortly after vaccine administration, have also been reported less frequently.
There have been fewer than ten cases of Guillain-Barre syndrome reported in H1N1 vaccine recipients. These numbers are consistent with normal background rates of the illness. All the individuals have recovered.
Some deaths have been reported in people who have been vaccinated. These are all investigated by WHO, and so far in no case is there a direct link to H1N1 vaccine as the cause of death.
There have been no differences in the safety profile of inactivated vaccines with or without adjuvant, and infectious attenuated vaccines..
WHO concludes:
Although intense monitoring of vaccine safety continues, all data compiled to date indicate that pandemic vaccines match the excellent safety profile of seasonal influenza vaccines, which have been used for more than 60 years.
The influenza H1N1 outbreak in Mexico has been analyzed to provide information on the pandemic potential of the new virus strain. The estimates offer some insight into the transmissibility and severity of the virus but must be tempered with the understanding that there are still uncertainties about all aspects of the outbreak.
Influenza incidence is difficult to determine because most infections are not confirmed by laboratory tests. Consequently case estimates play an important role in understanding transmission and spread. In this study, the authors used mathematical models to calculate the number of infections in Mexico based on exportation of the disease by travelers. They estimate that 23,000 infections had occurred in the country by late April. From this number they calculated a case fatality ratio of 0.4%. I note that my own crude calculations yielded a similar number.
To determine the transmissibility of the virus the authors first attempted to pinpoint the start date of the outbreak. One estimate is 15 February 2009 based on the first reported case in La Gloria. But the authors have another method as well:
An alternative approach to estimating the start date of the outbreak is to look at the diversity in the genetic sequences of viral samples collected from confirmed cases, assuming that diversity accumulates according to a molecular clock model.
The authors went on to compare 23 viral HA gene sequences from the Mexican outbreak. Readers of virology blog will understand the reference to a ‘molecular clock’ in the previous paragraph, having read previous posts on the error-prone nature of RNA virus replication. These approaches allow an estimation of the onset of the outbreak in Mexico to 12 January 2009. In other words, an influenza virus with a genome sequence that is the most common ancestor to those represented by the 23 HA gene sequences was circulating in humans in Mexico in January of this year.
The start date of the epidemic and the total number of infections can then be used to calculate the reproductive number, R0. This is the average number of secondary infections that result from one infected host in an otherwise uninfected population. In general, if R0 is less than 1, it is impossible to sustain an epidemic. If R0 is high, an epidemic is almost certain. Very high R0 values are typical of diseases with ‘super-spreaders’, such as the individual who transmitted SARS to others in the Hotel Metropole.
An R0 of 1.4 – 1.6 was calculated for the Mexican outbreak, which means that 14 to 73 generations of human to human transmission took place as of the end of April. This number is higher than observed for seasonal influenza, but in line with estimates from influenza pandemics of 1918, 1957, and 1968.
Fraser, C., Donnelly, C., Cauchemez, S., Hanage, W., Van Kerkhove, M., Hollingsworth, T., Griffin, J., Baggaley, R., Jenkins, H., Lyons, E., Jombart, T., Hinsley, W., Grassly, N., Balloux, F., Ghani, A., Ferguson, N., Rambaut, A., Pybus, O., Lopez-Gatell, H., Apluche-Aranda, C., Chapela, I., Zavala, E., Guevara, D., Checchi, F., Garcia, E., Hugonnet, S., Roth, C., & , . (2009). Pandemic Potential of a Strain of Influenza A (H1N1) : Early Findings Science DOI: 10.1126/science.1176062