There is currently intense media focus on “bird flu,” technically referred to as “Avian Influenza Virus Type A/H5N1.”

Experts have offered a broad range of views about this virus’s potential to cause widespread illness in humans. There is no debate, however, that the virus causes lethal infections in birds and is spreading rapidly around the globe.

As of April 11, 2007, 172 people have died from the virus (click here for the most recent update from the WHO). Most human cases have resulted from direct contact with infected birds. In an effort to protect human populations, hundreds of millions of domesticated birds have been vaccinated or destroyed.

While some authorities, including Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID) and the U.K.’s Chief Science Advisor, Sir David King, believe the risk to the human population is currently low, others remind us that influenza pandemics (serious worldwide outbreaks of flu) historically occur every 30 to 50 years. Even the relatively “mild” pandemics of 1957 and 1968 claimed a total of 3 million lives, while the 1918 “Spanish Flu” pandemic killed at least 20 million people and according to some experts, perhaps as many as 80 million, worldwide.

For a period of time, the spread of the flu was so extensive that the countries fighting World War I were forced to stop recruiting new soldiers because sending them into crowded training camps could be even more deadly than sending them onto the battlefield.

Pandemics Are Caused by Type A Influenza Viruses

All pandemic influenza episodes to date have been associated with type A flu viruses, although some type B strains can also cause serious illness.

Hemagglutinin and Neuraminidase projections are clearly seen on this computer simulation of an H5N1 influenza virus. Courtesy of 3DScience.com.

Type A influenza viruses are further classified by the specific configuration of two surface proteins, hemagglutinin and neuraminidase, that project from the virus (see illustration). These define the virus's particular HN subtype. See the Understanding Influenza page for more details.

The current avian flu is of subtype H5N1. However, new strains of the H5N1 virus are developing as the virus changes via genetic drift and the integration of new genetic information from the animals it infects. For instance, an H5N1 strain in Vietnam may be resistant to treatment with standard anti-influenza drugs like Tamiflu^® while some H5N1 strains in other locations may still respond favorably to therapy.

What is “bird flu” and why are so many people concerned about it?

Many strains of influenza infect birds and are therefore referred to as “avian influenza viruses” or, more casually, “bird flu.” Often, birds carry these viruses in their intestinal tracts without developing illness. Every so often, however, an avian flu virus changes into a form that causes disease within the bird population. Because of their seasonal migrations, it’s easy for an avian virus to rapidly spread around the world, infecting both wild birds and domestic poultry.

Martens are among the animals that have been cross-infected with the avian H5N1 virus.

Unlike human influenza, which primarily targets the respiratory system, birds develop influenza infections in their intestines. As a result, their droppings can contain high levels of the virus. In Europe, there have been recent reports of cats, civets and stone martens becoming infected with H5N1, presumably after eating dead birds or having contact with infected droppings. Most of these cross-infected animals have become ill from the virus and died.

However, the possibility exists that some animals cross-infected in this way may become “silent carriers,” able to infect others, possibly even humans, without having first raised suspicion because of their own lack of symptoms. At least one infected cat tested in Germany was found to be a silent carrier, prompting several European governments to advise pet owners to exercise caution, to keep their animals indoors and avoid close contact with their pets, such as sharing sleeping quarters. One particular fear is that even though these animals shed a much smaller quantity of the virus than infected birds, pet owners will often closely tend their sick animals, potentially exposing themselves to a greater risk of infection.

Jumping Species: Birds, Pigs and Humans

Historically, most avian influenza viruses that have shifted to become human pathogens first appeared in Southern China – including the misnamed 1918 Spanish Flu. Some experts suggest that this is because it is a common farming practice in the region to raise ducks and other birds out of doors, in close proximity with pigs. When the birds become infected, they can rapidly pass their avian viruses to the pigs through food and feces.

Unlike most animals, pigs can play host to both human and avian influenza viruses. A pig infected with both human and bird strains can provide the virus with a chance to mix and match genetic information in a process called “reassortment.” Sometimes, a reassortment will occur that combines the disease causing properties of the avian flu with the infectious properties of the human flu. These new strains then become a cause for serious concern.

For many years, it was thought that the ability of a virus to rapidly change and cause infection in new species, including humans, was the result of random or “Darwinian” mutations. It is now understood that the much more sophisticated process of genetic reassortment plays an important role in the development of new human viruses and their potential to cause pandemics. By picking up and integrating new genetic codes from other viruses within the organisms they infect, viruses actually learn how to create better opportunities for their own reproduction. From the virus’s point of view, this is simply a superior adaptation to its environment. From an infected organism’s point of view, this manifests as a more serious illness.

Ironically, when a new strain of influenza starts to become less pathogenic, it may actually become more dangerous. This is because a less provocative virus can survive, undetected, in a larger number of people and therefore spread more widely. Recent tracking of the H5N1 avian influenza shows that the mortality rate has started to decrease in some areas, including Vietnam – the epicenter of H5N1 infection in humans. While some take this as a positive indication that the virus is on the wane, others, including World Health Organization epidemiologist Peter Horby caution that the virus may be preparing to become more broadly distributed through the human population.

Exposure, Infection and Illness

As described in Understanding Viruses, several steps must take place before any given virus can cause illness.

• First, there must be exposure to the virus.
• Second, the virus must find a way to bind to cells, enter them and release their genetic material.
• Third, the virus must, for some period of time, use the cell’s DNA to copy itself more quickly than the immune system or therapeutic interventions can control it.

So far, the avian H5N1 influenza virus is not easily transmitted from animals to humans or from one human to another. Recent findings suggest that part of the reason is that the cells of the upper airway do not present a very good binding target for the virus, while those lower down in the respiratory tract are more vulnerable. This may be why only persons in prolonged and close contact with infected birds – or animals that came in contact with dead or infected birds or their droppings – have developed the illness.

Research has shown that the active ingredients in ViraWall – allophycocyanin and C-phycocyanin – inhibit the ability of certain viruses to replicate and damage cells. Current thinking is that these proteins may block these viruses from being able to enter cells and use them for reproduction. This is important because a virus cannot survive and reproduce without access to a living cell. It must first be admitted to a living cell by a process called viral endocytosis. Once inside, the virus splices its genetic material into the host cell's DNA and directs it to turn out new copies. Eventually, the host cell either bursts, sending out numerous copies of the virus that can infect other cells, or new copies bud from the infected cell’s membrane, as shown..

If a substance, like ViraWall, can block some viruses from entering cells, it may support the body’s natural methods for dealing with viral challenges. Even if the action is not complete, slowing down the rate of cellular entry may give the immune system a better chance to engage its natural virus fighting capabilities. These may include the production of natural killer and cytotoxic T cells through the so-called Th1 or “cell-mediated” arm of the immune system, or the production of specialized virus fighting chemicals such as RNase-L and interference RNA.

Illustration of how an RNA virus enters a cell and replicates. Adapted from the National Cancer Institute.

A Raging Cytokine Storm

A mild flu season can claim thousands of lives – a pandemic literally kills millions. Those who succumb are most often the elderly and frail, the very young, or those whose immune systems have been compromised in some significant way.

But some flu viruses, including the 1918 pandemic and the current H5N1 virus, do something more pernicious. Many of those who are hit hardest are young and otherwise healthy. This tragic irony may occur in part because these viruses are thought to trigger immune system reactions that are so intense and uncontrolled researchers call them “cytokine storms.” In this instance, having a “strong” immune system may actually be a disadvantage.

Fluorescent markers reveal different cytokine responses in human lung cells with exposure to different influenza viruses. Image adapted from Chan MCW et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respiratory Research 2005, 6:135, (accessed April 12, 2006)

Cytokines are chemicals naturally produced in the body that comprise a sophisticated signaling system. Certain cytokines are produced in response to viral infection and tell the body to gear up specific types of immune defenses. Other cytokines are produced to mount inflammatory reactions to help control the virus. In the case of H5N1 infection, these immune signals become wildly over-stimulated. Caught up in a raging “cytokine storm,” infected individuals may literally be killed by their own over-zealous inflammatory immune system responses.

The 1918 Spanish Flu caused extremely powerful cytokine reactions, yet only an estimated 2.5% of those who became infected died. The mortality rate for H5N1 avian flu infection is currently 59% - 172 deaths have resulted from 291 reported cases (World Health Organization figures as of April 11, 2007). Clearly, anything that interrupts the progression from viral exposure to full-scale illness may be helpful, especially since the complex consequences of an established viral infection, including the body’s own immune responses, may become very difficult to control.

This observation illustrates why it’s important to consider not only viral exposure and cellular infection but also the complex interactions of a pathogen such as H5N1 with the immune system and other physiological characteristics of the body.

A word of caution: Experts warn that certain natural remedies that stimulate the immune system may actually run the risk of exaggerating this unbalanced cytokine reaction. For example, many medicinal mushrooms have been shown to increase the production of specialized immune system cells and their associated cytokines including alpha-TNF (tumor necrosis factor) and various interleukins. While these may have some value in combating viruses and cancerous cells, some of these otherwise beneficial substances might, in the case of an H5N1 influenza, further over-stimulate dangerously unbalanced inflammatory reactions. For this reason, it’s always best to work with a healthcare professional who understands the relevant subtleties of immune system pathways and potential reactions.

Please note that this information is provided for educational purposes only and is not intended to act as a substitute or replacement for proper health and medical advice from a trained and licensed professional healthcare provider. If you are ill, or are concerned about your health, please contact an appropriate healthcare professional.