virology blog
About viruses and viral disease
On This Week in Virology episode #17, Vincent, Dick, and guest Saul Silverstein talk about discoveries in virology that have had a major impact on the field. By seminal, we mean “strongly influencing later developments”.
Click the arrow above to play, or right-click to download TWiV #17
The third edition of Principles of Virology has just been published by ASM Press. Written by  S. J. Flint, L. W. Enquist, V. R. Racaniello, and A. M. Skalka, it is now two volumes to make it easier to handle and carry in backpacks, bags, and briefcases. Of course, the textbook is also completely revised and updated to reflect important advances in the field. The textbook continues to fill the gap between introductory texts and advanced reviews of major virus families. These two volumes provide upper-level undergraduates, graduate students, and medical students with a state-of-the-art introduction to all aspects of virology.Â
President-elect Barack Obama has named Harold Varmus as a co-chair of the Presidents’ Council of Advisors on Science and Technology (PCAST), a team that will work with White House science adviser John Holdren. Varmus won a Nobel Prize in 1989 for his work on elucidating how retroviruses cause transformation of cells. He is currently president and chief executive officer of New York’s  Memorial Sloan-Kettering Cancer Center. Previously, Varmus served as director of the US National Institutes of Health. During his tenure there, the NIH research budget doubled, underscoring his enthusiasm for scientific research. His presence on PCAST is an auspicious sign that the Obama administration will revitalize the US research community.
Also named to PCAST with Varmus is Eric Lander, Professor of Biology at MIT, a well known scientist who is exploring the use of the human genome in medicine.
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Yesterday, 18 December, marked 100 years since Karl Landsteiner, MD and his assistant E. Popper, identified the viral etiologic agent of poliomyelitis. According to A History of Poliomyelitis by JR Paul:
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…at a medical meeting in Vienna on December 18, 1908, the immunologist Landsteiner and his assistant Popper were able to demonstrate microscopic slides of one human and two monkey spinal cords, all showing the familiar histological picture of acute poliomyelitis. Sections from the human infection came from a boy of nine years who had died after an illness of three days. Bacterial cultures of the spinal cord had been sterile, and injection of a suspension of the ground-up cord into rabbits, guinea pigs, and mice also had given negative results. But the team went further than this in their choice of experimental animals. They selected the right ones in the form of two monkeys, animals which probably represented an expensive luxury for these young scientists. Nevertheless, they were willing to risk what might have been considered a useless expense for an experiment which did not have any particular promise of success. The monkeys were of different species, one being a Cynocephalus hamadryas and the other a Macaca rhesus (Macaca mulatta). The choice turned out to be fortunate. Both of these species of primates are known today to be highly susceptible to experimental poliomyelitis, although to somewhat different degrees. The selection of Old World monkeys rather than the relatively insusceptible New World ones was just as fortunate.
The bacteriologically sterile material obtained from the spinal cord of the fatal human case was injected into the two animals intraperitoneally. The Cynocephalus monkey succumbed eight days later… The real test came when histological sections of the spinal cord revealed typical and extensive lesions which had a remarkably close resemblance to the lesion of human poliomyelitis. Similar, though not such widespread, changes were found in the sections of the cord from the second monkey, which developed complete flaccid paralysis of both legs… The authors must have been amazed, and not a little pleased, at the nature of the experimental disease produced in this animal, which resembled so closely the paralytic disease in man. They made the modest suggestion that poliomyelitis might be caused by an invisible virus, an opinion soon confirmed by other experiments.
The identification of poliovirus was an enormous advance that ultimately lead, 50 years later, to the development of two effective vaccines. The use of these vaccines has nearly eradicated poliomyelitis from the globe. Yesterday was truly an important day in virology and medicine.
Virologist D. Carleton Gajdusek, who was awarded the 1976 Nobel Prize in medicine for unraveling the nature of the prion disease Kuru, has died, as reported by the New York Times.
Gajdusek’s work on Kuru, a fatal encephalopathy found in the Fore people of New Guinea, proved that human transmissible spongiform encephalopathies (TSEs) could be transmitted among humans. This group of rare, slow diseases now includes Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome in humans, as well as bovine spongiform encephalopathy (BSE, or mad cow disease) and scrapie in sheep and goats. These disorders are rare, but always fatal. Gajdusek’s contribution was to understand that the fatal encephalopathy affecting the Fore people was spread among women and children by ritual cannibalism of the brains of deceased relatives. The disease stopped when cannibalism was discontinued.Â
Subsequent work by others showed that the infectious agents of TSEs are highly unconventional because they lack nucleic acid genomes. Stanley Prusiner called the agent of scrapie a ‘prion’ and suggested that an misfolded form of the protein causes the fatal encephalopathy. The genomes of many animals, including humans, carry a gene called prnp (encoding the PrP protein) which is essential for the pathogenesis of TSEs. In the simplest case, the misfolded PrP protein (PrPsc) converts normal PrP protein to more copies of the pathogenic form. The altered protein may be acquired by infection, by inheritance of the prnp gene with an autosomal mutation, or sporadically. It is believed that Kuru was established in the small Fore population when the brain of an individual with sporadic CJD was eaten.
I met Dr. Gajdusek briefly in the 1980s when he presented a seminar at Columbia. We were in a room alone for about 5 minutes, awaiting the arrival of other participants in the post-seminar dinner. In that short time it became clear that he was extremely intelligent, but not at all interested in my work on poliovirus, much to my disappointment.
Today’s NY Times reports that cases of wild polio (as opposed to vaccine-induced polio) are appearing in new countries, and increasing numbers are occurring in countries that are endemic for the disease. Article link here. A disease is ‘endemic’ in a country when it is maintained without introduction from other countries.
Polio is considered to be endemic in four countries: Nigeria, India, Afghanistan, and Pakistan. The reasons for the continued presence of the disease in these countries are complex. Armed conflict in Afghanistan and Pakistan has prevented adequate immunization. The outbreak in Nigeria is a consequence of the government’s decision to halt immunization several years ago. Administration of polio vaccine has since been resumed, but the spread of type 1 poliovirus still occurs. In India, repeated immunization in western Uttar Pradesh often fails to prevent infection, for obscure reasons.
The number of cases of polio in these four countries has risen since the same time last year. In India, there have been 486 cases so far this year, compared with 326 by this time in 2007. The same increases are seen in Pakistan (81 vs. 16), Nigeria (728 vs. 210), and Afghanistan (22 vs. 12).
Unfortunately, the disease is also spreading to other countries. For example, two cases have been reported in Ghana, which had not reported the disease since 2003. Overall there have been 1406 cases reported globally this year, compared with 635 by this time in 2007. More details can be found at polioeradication.org.
The reason for the increased case count is unknown, especially because WHO sponsored immunization programs continue at an aggressive rate.
Remember, for every reported case of polio, there are likely at least 100-200 individuals harboring the virus without showing symptoms of paralysis. These asymptomatic infections are important for the transmission of the infection.