TWiV 374: Discordance in B

TWiVOn episode #374 of the science show This Week in Virology, the TWiVniks consider the role of a cell enzyme that removes a protein linked to the 5′-end of the picornavirus genome, and the connection between malaria, Epstein-Barr virus, and endemic Burkitt’s lymphoma.

You can find TWiV #374 at

TWiV 367: Two sides to a Coyne

On episode #367 of the science show This Week in Virology, two Coynes join the TWiV overlords to explain their three-dimensional cell culture model of polarized intestinal for studying enterovirus infection.

You can find TWiV #367 at

TWiV 328: Lariat tricks in 3D

On episode #328 of the science show This Week in Virology, the TWiVocateurs discuss how the RNA polymerase of enteroviruses binds a component of the splicing machinery and inhibits mRNA processing.

You can find TWiV #328 at

TWiV 290: Baylor goes viral

On episode #290 of the science show This Week  in VirologyVincent meets up with Janet Butel and Rick Lloyd at Baylor College of Medicine to talk about their work on polyomaviruses and virus induced stress.

You can find TWiV #290 at

Coxsackie NY and the virus named after it

coxsackie-nyRecently while driving north on the New York State Thruway I passed the exit for the town of Coxsackie, NY (population 8,884). I grabbed my camera and photographed the exit sign, and reminded myself to write about the virus named after this small town.

In the summer of 1947 there were several small outbreaks of poliomyelitis in upstate New York. Gilbert Dalldorf, the director of the Wadsworth Laboratory in Albany, NY, and his associate Grace M. Sickles investigated this outbreak. In particular they sought polioviruses that could replicate in mice. This search was motivated by the fact that research on poliovirus required the use of monkeys which were extremely expensive. Dalldorf had attended the Fourth International Congress for Microbiology in 1947 where he heard that very young mice – suckling mice – could readily be infected with Theiler’s virus.

Dalldorf and Sickles made fecal suspensions from two children suspected of having poliomyelitis, and inoculated these into adult and suckling mice. Only the suckling mice (1 – 7 days old) developed paralysis; animals more than one week old were resistant to infection. The damage responsible for limb paralysis was widespread lesions in skeletal muscles, not in the central nervous system as occurs with poliovirus. Further study revealed that the viruses could be distinguished serologically from poliovirus.

Not only had Dalldorf and Sickles identified the first members of a very large group of human viruses, but they also introduced and popularized a new and inexpensive animal into the virology laboratory – the suckling mouse. In 1949 Dalldorf suggested that the new viruses be called Coxsackie viruses, because the first recognized human cases were residents of that New York village. This unique name is of native North American origin.

Over ten years later the importance of this work was recognized by Dr. Max Finland of Boston City Hospital:

The isolation by Dalldorf and Sickles of viruses which produced paralysis with destructive lesions of muscle in sucking mice and hamsters, from the stools of two children with signs of paralytic poliomyelitis was an achievement that may rank in importance with Landsteiner and Popper’s production of human poliomyelitis in monkeys.

In subsequent years many different Coxsackieviruses were isolated that cause a variety of clinical syndromes. Today at least 30 serotypes of Coxsackieviruses are classified in the enterovirus genus of the Picornaviridae. The viruses are classified into groups A or B depending upon the pathological effect in suckling mice.

Not every locale is pleased to have a virus named after it. In May 1993, an outbreak of an unexplained pulmonary illness occurred in the southwestern United States, in an area shared by Arizona, New Mexico, Colorado and Utah called “The Four Corners.” Muerto Canyon was proposed as the name for the etiologic agent of the disease, because the virus was first isolated from a rodent near the canyon. However after residents objected, the name Sin nombre virus was given to the agent of hantavirus pulmonary syndrome.

Dalldorf G, & Sickles GM (1948). An Unidentified, Filtrable Agent Isolated From the Feces of Children With Paralysis. Science (New York, N.Y.), 108 (2794), 61-62 PMID: 17777513

Hand, foot, and mouth disease outbreak in China

hand-foot-mouth-diseaseAn outbreak of hand, foot, and mouth disease in China has lead to 41,000 infections and 18 deaths this year. What is this disease and what causes it?

Hand, foot, and mouth disease (HFMD) is a rather common viral infection of children. There were 80,000 recorded cases of the disease just in China for 2007. The disease occurs globally, displaying seasonality (summer, early autumn) in temperate climates. It is caused by members of the genus enterovirus, Coxsackievirus A10 and A16 or enterovirus type 71, viruses that are related to poliovirus. The virions are composed of a positive-sense RNA surrounded by a capsid built with four different viral proteins. The predominant virus in the 2007 outbreak in China was enterovirus type 71. The identify of the virus causing the current outbreak is not known, but enterovirus 71 has already been identified in several patients.

HFMD is typically acquired through close contact with an infected individual. It begins with nonspecific symptoms such as fever and malaise, and is followed by the development of ulcerating sores on the tongue, gums, and insides of the cheeks. A skin rash then appears on the hands and soles of the feet. The infection is spread to others by the virus that is present in pharyngeal secretions, saliva, and fluid from the skin blisters.

Outbreaks of HFMD typically involve children because they are not immune to infection, and because children physically intereact in ways that promote transmission, especially in summer months when outdoor play is common. The disease is much less prevalent in adults because they are protected by immunity conferred by childhood infection.

HFMD is an acute viral infection which resolves within 1-2 weeks. When caused by Coxsackieviruses, the course of the disease is usually uneventful. However, enterovirus 71 can enter the central nervous system where it may cause encephalitis or a polio-like paralysis. How the virus reaches this site is not known. By analogy with poliovirus, we assume that the virus enters the bloodstream – possibly after replicating in the intestine – and then makes its way to the spinal cord. This virus has emerged as a significant neurological pathogen in Taiwan.

There are no vaccines or antiviral drugs available for treatment of HFMD, and little research is done on the viruses that cause the disease. This situation is likely to change with the emergence of enterovirus 71 as the most significant neurotropic enterovirus in some areas of the world.

Zhang, Y., Tan, X., Wang, H., Yan, D., Zhu, S., Wang, D., Ji, F., Wang, X., Gao, Y., & Chen, L. (2009). An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China Journal of Clinical Virology, 44 (4), 262-267 DOI: 10.1016/j.jcv.2009.02.002

QIU, J. (2008). Enterovirus 71 infection: a new threat to global public health? The Lancet Neurology, 7 (10), 868-869 DOI: 10.1016/S1474-4422(08)70207-2

Arita, M., Wakita, T., & Shimizu, H. (2008). Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity Journal of General Virology, 89 (10), 2518-2530 DOI: 10.1099/vir.0.2008/002915-0