virology blog

About viruses and viral disease

Norovirus Gastroenteritis

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From KSL-TV – Salt Lake City, UT, USA:

“More than 130 people have contracted the Norovirus, a stomach illness, at Yellowstone National Park this summer. The Park’s concession workers and housekeepers were hit the hardest.

“Norovirus is the same illness that sickened hundreds of cruise ship passengers earlier this year.”

Contrary to what the article reports, Norovirus is not an illness; it is a virus. The illness it causes, the ‘stomach illness’ reported above, is known as gastroenteritis – inflammation of the lining membrane of the stomach and the intestines. Therefore the correct way to have written the first sentence of the news report above would be “More than 130 people at Yellowstone National Park have contracted a stomach illness caused by Norovirus…”

The lesson here is that it is always important to distinguish the virus from the disease, something that journalists often have a problem with.

Noroviruses are important human pathogens; they cause over 90% of all cases of nonbacterial gastroenteritis. Outbreaks of Norovirus gastroenteritis often occur on cruise ships or in resort settings. The infection is usually acquired by ingesting contaminated food. Typically, the food is contaminated by a worker who is infected with Norovirus and either has no symptoms or has already recovered and is still shedding virus. If the food handler does not properly wash after using the bathroom, his/her hands may be contaminated with fecal matter which contains many virus particles.

What is a virus?

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Viruses are distinct biological entities with the following properties:

1. A virus is an infectious, obligate intracellular parasite.

2. The genetic material of a virus is either DNA or RNA.

3. The genetic material of a virus enters a host cell and directs the production of the building blocks of new virus particles (called virions).

4. New virions are made in the host cell by assembly of these building blocks.

5. The new virions produced in a host cell then transport the viral genetic material to another host cell or organism to carry out another round of infection.

Viruses are easy to understand when we reduce their properties to simple descriptions such as those listed above. The confounding issues lie in the details – and with viruses, there are many, many details.

HIV, AIDS, and Condoms

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In October 2003, the Vatican published a paper claiming that the HIV virus can pass through latex condoms and cause infection. I have not seen the original paper, but have read about some of its points in various online newsreports, such as this one from BBC News World Edition. In this report, Cardinal Alfonso Lopez Trujillo, president of the Vatican’s Pontifical Council for the Family, claims that causative agent of AIDS, HIV-1, can pass through small pores in the condom. I would like to see the ‘scientific evidence’ supposedly in this report, but I have no doubt that it is entirely wrong. HIV-1 virions are very small, but latex is not sufficiently porous to allow the virions to pass through. It is quite clear that the proper use of condoms is highly effective at preventing spread of this virus.

In fact, as long ago as 1992, the question of whether or not HIV-1 virions could pass through latex was discussed in the Washington Times. A good synopsis of these issues can be found in The Straight Dope.

The Vatican report has been roundly criticised by a wide range of individuals, from scientists to religious leaders. Yet, the Vatican refuses to reverse their position. Clearly this is an example of how the Vatican’s position on birth control – all forms being unacceptable except ‘rythmn’ – is clouding their view on the health and safety of millions of people. Many will believe the Vatican, and stop using condoms, which will only increase transmission of the disease.

The Vatican does not want people to use condoms, but it is highly irresponsible for them to use HIV-1 and AIDS as a means of discouraging their use. Especially when the excuse for not using condoms – that they pass the virus – is categorically wrong. In the end, more people will contract AIDS as a consequence of the Vatican’s pronouncement. Shouldn’t the Vatican be trying to save lives?

Poliovirus is IRESistable

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Our latest paper has just been published in the Journal of Clinical Investigation. The title of the paper is “Poliovirus tropism and attenuation are determined after internal ribosome entry”. This is the work of a Ph.D. student in my laboratory, Steven Kauder.

If you would like a nice summary of this work, there is an excellent commentary by Bert Semler in the same journal, entitled “Poliovirus proves IRES-istible in vivo“. The title of this commentary is a play on the main theme of the research paper: the Internal Ribosome Entry Site (IRES) of poliovirus. The poliovirus IRES is an RNA sequence at the 5′-end of the viral genome that allows ribosomes to bind internally, rather than threading on the 5′-end as they do for most mRNAs. In our paper, we show that poliovirus attenuation and tropism are not determined by the viral IRES.

Let’s back up a bit to explain this last statement. Viral tropism is defined as the tissues in which a virus replicates. Poliovirus, the causative agent of poliomyelitis, infects very few tissues in humans: the intestine, the brain and spinal cord, and perhaps one other site. A restricted tropism is in fact a common property of many viruses. What restricts viral multiplication to so few tissues has been a long-standing question in virology. For poliovirus, it was first believed that the restricted tropism was a consequence of where the virus receptor is located. The virus receptor is a cell surface protein that is needed to bind the virus particle and bring the genetic material of the virus into the cell. However, some time ago it was shown that the receptor for poliovirus does not determine the narrow tropism of the virus. Subsequently it was suggested that the viral IRES might control the tropism – but in this recent paper we show that this is not the case.

The other topic of our paper concerns the live poliovirus vaccine, also known as the Sabin vaccine or oral poliovirus vaccine (OPV). There are three different vaccine strains of poliovirus, all isolated by Albert Sabin. The genetic material of each vaccine strain contains mutations, or genetic changes, that prevent it from causing disease. When the Sabin vaccines are ingested, they replicate in the intestine and provide immunity to infection, but they do not cause polio. Precisely how these mutations ‘work’ has been a matter of considerable debate. It has been believed that the mutations change the properties of the viral IRES so that it continues to direct translation in the human gut, but not in the spinal cord and brain. In our paper we show that this hypothesis is wrong. A mutation in one of the three Sabin vaccine strains actually weakens the virus in all tissues.

I recognize that much of this description may be beyond the understanding of someone who is not a scientist. A goal of this weblog is to make virology accessible to everyone. Therefore in the coming weeks I will endeavor to provide the background needed to understand this and similar material that will appear here.

The Bioterror Boondoggle

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Scientists who conduct research on viruses depend heavily on outside sources of funding to staff and supply their laboratories. One of the major sources of funding for independent research is the National Institutes of Health. Funds for research are allocated through a grant mechanism in which investigators submit detailed proposals for the work they wish to carry out. The proposals are reviewed by a panel of experts and graded, and the best proposals are funded.

This type of NIH-funded investigator-initiated basic research has proven enormously successful since the 1950s. The best innovation comes when scientists decide what they wish to work on. From the most obscure beginnings have emerged discoveries that have revolutionized medicine. For example, research on bacteria and viruses that infect bacteria lead to the development of recombinant DNA technology. This technology forms the basis for many of today’s blockbuster drugs and diagnostic tests.

As a consequence of the release of Bacillus anthracis (a bacterium) in the U.S. in 2001, the NIH has shifted some of its resources towards work on viruses, fungi, and bacteria that could be used for bioterrorism. In addition, the NIH has adopted what it calls a ‘roadmap‘, in which it identified the most important areas of medical research that investigators should focus on.

I have problems with both of these issues, e.g. diverting NIH funds to bioterrorism research, and establishing a ‘roadmap’. A few months ago, Alan Dove, a freelance science writer, asked my opinion on the recent shift in focus at NIH, and snippets of my responses have appeared in this week’s Nature Medicine.

My thoughts on bioterrorism research will need a separate post. Meanwhile, here is my complete response to Alan Dove’s question:

“The first problem is that NIH has never been good at deciding what to work on. Drugs and vaccines are fine; but as far as basic research goes, who is to say what should be done? The best work comes from letting scientists follow their own paths. Find a good scientist, give ’em money, and you’ll get good science. That’s where recombinant DNA came from, if I recall. In today’s climate, the NIH is not likely to put a high priority on, say, phage research; but one could argue that it might still have unseen surprises that are widely applicable. I don’t think anyone is smart enough to predict what to work on, the current NIH leadership included.

“On the other hand, I think it’s great if the NIH wants to fund development of drugs and vaccines that are third-world problems and not likely to get the attention of US pharma. In fact, I think all drug and vaccine development should be out of the private sector, but I understand that is heretical and not a capitalistic view. Drug and vaccine development should not be driven by profit, but by need. The only way to deal with this is to have the government do the work – at the NIH, or extramurally.

“I’m not worried about diverting a good part of the NIH budget for these purposes. The effect will certainly be to divert money away from investigator-initiated research, e.g. RO1 grants. For the next five years, it will be hard to get grants; but everything cycles and I expect that at some point it will become less difficult.

“I do think it is important to be smart about what the NIH decides to direct its money towards. I’m not sure that scientific logic prevails; probably politics are playing too great a role. Politicians need to tell their constituents how they spend their tax dollars; it’s easy to point out a shiny new jet fighter, but not so easy to point out what the NIH does. Hence, ‘directed research’. Here everyone, we are making an AIDS vaccine, or a TB drug. But pouring money into ‘biodefense’ research is just a load of crap. We really have to focus only on anthrax and smallpox – nothing else is likely to work very well and I defy anyone to engineer a virus or bacterium to be more lethal than it already is. Biodefense research is just another political ploy and a waste of NIH dollars.”

Are Viruses Living?

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Let’s first define life. According to the online Merriam-Webster Dictionary, life is “an organismic state characterized by capacity for metabolism, growth, reaction to stimuli, and reproduction.”

Viruses are not living things. Viruses are complicated assemblies of molecules, including proteins, nucleic acids, lipids, and carbohydrates, but on their own they can do nothing until they enter a living cell. Without cells, viruses would not be able to multiply. Therefore, viruses are not living things.

When a virus encounters a cell, a series of chemical reactions occur that lead to the production of new viruses. These steps are completely passive, that is, they are predefined by the nature of the molecules that comprise the virus particle. Viruses don’t actually ‘do’ anything. Often scientists and non-scientists alike ascribe actions to viruses such as employing, displaying, destroying, evading, exploiting, and so on. These terms are incorrect because viruses are passive, completely at the mercy of their environment.

Update: See a more recent post for my thoughts on this question.