Table of Contents:

Foreword

Introduction

I. Storm Gathering

1. 1918

2. Master of Metamorphosis

3. H5N1

4. Playing Chicken

5. Worse Than 1918?

6. When, Not If

II. When Animal Viruses Attack

1. The Third Age

2. Man Made

3. Livestock Revolution

4. Tracing the Flight Path

5. One Flu Over the Chicken's Nest

6. Coming Home to Roost

7. Guarding the Henhouse

III. Pandemic Preparedness

1. Cooping Up Bird Flu

2. Race Against Time

3. Tamiflu

IV. Surviving the Pandemic

1. Don't Wing It

2. Our Health in Our Hands

3. Be Prepared

V. Preventing Future Pandemics

1. Tinderbox

2. Reining in the Pale Horse

Topics

References 1-3,199

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Influenza virus

Viruses like influenza have only about a week to proliferate before the host kills them or, in extreme cases, they kill the host. During this contagious period there may be a natural selection toward viruses of greater virulence to overwhelm host defenses. Our bodies fight back with a triple firewall strategy to fend off viral attackers. The first is our set of barrier defenses.

The outermost part of our skin is composed of 15 or more layers of dead cells bonded together with a fatty cement.154 A new layer forms every day as dead cells are sloughed off, so about every two weeks, the entire layer is completely replaced.155 Since viruses can only reproduce in live functional cells and the top layers of skin are dead, our intact skin represents a significant barrier to any viral infection.

But the respiratory tract has no such protection. Not only is our respiratory tract lined with living tissue, it represents our primary point of contact with the external world. We only have about two square yards of skin, but the surface area within the convoluted inner passageways of our lungs exceeds that of a tennis court.156 And every day we inhale more than 5,000 gallons of air.157 For a virus, especially one not adapted to survive stomach acid, the lungs are the easy way in.

Our bodies are well aware of these vulnerabilities. It’s not enough for a virus to be inhaled; it must be able to physically infect a live cell. This is where mucus comes in. Our airways are covered with a layer of mucus that keeps viruses at arm’s length from our cells. Many of the cells themselves are equipped with tiny sweeping hairs that brush the contaminated mucus up to the throat to be coughed up or swallowed into the killing acid of the stomach. One of the reasons smokers are especially susceptible to respiratory infections in general is that the toxins in cigarette smoke paralyze and destroy these fragile little sweeper cells.158

Our respiratory tract produces a healthy half-cup of snot every day,159 but can significantly ramp up production in the event of infection. Influenza viruses belong to the “orthomyxovirus” family, from the Greek orthos- myxa-, meaning “straight mucus.” The influenza virus found a way to cut through this barrier defense.

Unlike most viruses, which have a consistent shape, influenza viruses may exist as round balls, spaghetti-like filaments, or any shape in between.160 One characteristic they all share, though, is the presence of hundreds of spikes protruding from all over the surface of the virus, much like pins in a pincushion.161 There are two types of spikes. One is a triangular, rod-shaped protein called hemagglutinin.162 The other is a square, mushroom-shaped enzyme called neuraminidase.

There have been multiple varieties of both enzymes described, so far 16 hemagglutinin (H1 to H16) and 9 neuraminidase (N1 to N9). Influenza strains are identified by which two surface enzymes they display. The strain identified as “H5N1” denotes that the virus is studded with the fifth hemagglutinin in the WHO-naming scheme, along with spikes of the first neuraminidase.163

There is a reason the virus has neuraminidase jutting from its surface. Described by virologists as having a shape resembling a “strikingly long-stalked mushroom,”164 this enzyme has the ability to slash through mucus like a machete, dissolving through the mucus layer to attack the respiratory cells underneath.165 Then the hemagglutinin spikes take over.

Hemagglutinin is the key the virus uses to get inside our cells. The external membrane that wraps each cell is studded with glycoproteins—complexes of sugars and proteins—that are used for a variety of functions, including cell-to-cell communication. The cells of our body are effectively sugar-coated. The viral hemagglutinin binds to one such sugar called sialic acid (from the Greek sialos for “saliva”) like Velcro hooks on a loop. In fact, that’s how hemagglutinin got its name. If you mix the influenza virus with a sample of blood, the hundreds of surface hemagglutinin spikes on each viral particle form crosslinks between multiple sialic acid-covered red blood cells, effectively clumping them together. It agglutinates (glutinare or “to glue”) blood (heme-).166

The docking maneuver prompts the cell to engulf the virus. Like some Saturday Night Live “landshark” skit, the virus fools the cell into letting it inside. Once inside it takes over, turning the cell into a virus-producing factory. The conquest starts with the virus chopping up our own cell’s DNA and retooling the cell to switch over production to make more virus with a single-mindedness that eventually leads to the cell’s death through the neglect of its own needs.167

Why has the virus evolved to kill the cell, to burn down its own factory? Why bite the hand that feeds it? Why not just hijack half of the cell’s protein-making capacity and keep the cell alive to make more virus? After all, the more cells that end up dying, the quicker the immune system is tipped off to the virus’s presence. The virus kills because killing is how the virus gets around.

Influenza transmission is legendary. The dying cells in the respiratory tract trigger an inflammatory response, which triggers the cough reflex. The virus uses the body’s own defenses to infect others. Each cough releases billions of newly made viruses from the body at an ejection velocity exceeding 75 miles an hour.168 Sneezes can exceed 100 miles per hour169 and hurl germs as far away as 40 feet.170 Furthermore, the viral neuraminidase’s ability to liquefy mucus promotes the formation of tiny aerosolized droplets,171 which are so light they can hang in the air for minutes before settling to the ground.172 Each cough produces about 40,000 such droplets,173 and each microdroplet can contain millions of viruses.174 One can see how easily a virus like this could spread around the globe.

In terms of viral strategy, another advantage of the respiratory tract is its tennis court–sized surface area which allows the virus to go on killing cell after cell, thereby making massive quantities of virus without killing the host too quickly. The virus essentially turns our lungs into flu virus factories. In contrast, viruses that attack other vital organs like the liver can only multiply so fast without taking the host down with them.175