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About viruses and viral disease

West Nile Virus

5 August 2004 by Vincent Racaniello

For the past month or so, a search of Google News for ‘virus’ has yielded mainly articles on computer viruses or West Nile virus.

Why are there so many articles on West Nile virus? Summer is the prime season for transmission of this virus, which is spread to humans by mosquitoes.

In temperate climates (e.g. New York City), the mosquito season extends from April through October, when mosquitoes breed in polluted, standing water. The virus is maintained in birds (the reservoir of the virus) and transmitted among birds by mosquitoes. This bird-mosquito-bird pattern is known as an enzootic cycle.

West Nile virus may cause a serious disease in humans called viral encephalitis (inflammation of the brain). The virus was first isolated in the West Nile district of Uganda in 1937. It had not been isolated in the Western Hemisphere before 1999, when cases of West Nile virus encephalitis were identified in New York City. Since that first outbreak, the virus has spread across the United States, and is now invading Canada, Mexico, and the West Indies. All the Google News ‘hits’ on West Nile virus concern first isolations of the virus this season. For example: West Nile virus turns up in 42 Illinois counties, and West Nile virus found in three Bay Area Houston cities.

A fascinating, and unanswered question, is why the virus arrived in New York City in 1999. The New York strain of West Nile virus is very similar to a virus isolated from a goose in Israel in 1999. This virus might have been transported across the Atlantic Ocean in an infected bird, mosquito, human, or horse.

An excellent review article on West Nile virus and the disease it causes can be found in the Journal of Clinical Investigation.

Filed Under: Information

Antiviral Drugs

29 July 2004 by Vincent Racaniello

An article in The Star of Malaysia illustrates why the public is often confused by stories about viruses in the popular press.

The article reports that ‘a four-man medical research team from the University Malaya Medical Centre has achieved a first by discovering an anti-virus for dengue fever from herbs’.

Let’s take apart this sentence to understand what it means.

Dengue fever is a disease caused by Dengue virus. It is transmitted by mosquitoes and is endemic (restricted to a locality or region) in the Caribbean, Central and South America, Africa, and Southeast Asia. It is an extremely important disease as billions of people in these areas are at risk. The first infection with Dengue virus is not often very serious (fever, severe headache, back and limb pain, rash). The problem arises when a person is infected a second time, when a fatal disease, called dengue shock syndrome, may occur. As a result of the serious nature of dengue shock syndrome, much effort is being devoted to producing vaccines and antiviral drugs to prevent the disease.

As is so typical for science reporting in many newspapers, this article provides little information on what exactly has been done. We are only told that the team has discovered an ‘anti-virus…from herbs’. I speculate that they have found that an extract from a plant can block virus infection. The article further suggests that capsules containing this anti-Dengue virus drug will be available early next year.

What exactly have the investigators in Malaysia done? There are two general ways of discovering antiviral drugs. The oldest approach, called ‘blind screening’, involves searching through random chemicals and natural product mixtures (e.g. plant extracts) for compounds that block virus replication in cell cultures. When a ‘hit’ is obtained – in other words, a compound that blocks virus replication in cells – it is further tested for safety and efficacy in animals. The specific inhibitory molecule is identified and perhaps further modified to reduce toxicity and improve efficacy. After testing hundreds or thousands of compounds, the antiviral may then be evaluated in humans (clinical trials). One notable antiviral discovered in this way in the 1960s was amantadine (also known by the trade name Symmetrel), used to treat influenza infections. The second approach to identifying antiviral drugs iscalled ‘mechanism-based screening’; we’ll talk about that in a subsequent post.

Although plants are known to have medicinal effects, and indeed contain antimicrobial compounds, none have been reported in the scientific literature as having been tested against Dengue virus. I conclude that the Malaysian group has found that a crude extract of an herb inhibits Dengue virus replication in cells. To think that such extracts could be used directly in people is ludicrous. Plant extracts contain many different compounds and can even be toxic. It would be foolish to give such extracts to humans without purifying the anti-Dengue virus molecule – the side effects could be fatal.

Further increasing my skepticism of this report is the claim that this discovery is ‘a first’. A search of the scientific literature (PubMed) reveals that other antivirals against Dengue virus have already been described, although none have been used in humans.

There are at least two morals to this story. One, don’t always believe what you read in the paper. Two, safe and effective antiviral compounds are very difficult and costly to identify. Unfortunately, a Dengue antiviral is still many years away.

Filed Under: Information

Norovirus Gastroenteritis

29 July 2004 by Vincent Racaniello

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.

Filed Under: Information

What is a virus?

28 July 2004 by Vincent Racaniello

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.

Filed Under: Information

HIV, AIDS, and Condoms

1 July 2004 by Vincent Racaniello

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?

Filed Under: Commentary Tagged With: AIDS, condoms, HIV, viral, virology, virus, viruses

Poliovirus is IRESistable

16 June 2004 by Vincent Racaniello

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.

Filed Under: Information Tagged With: internal initiation, IRES, poliovirus, translation, tropism, viral, virology, virus, viruses

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