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This lesson will discuss variola virus, the virus that causes smallpox. You will learn the functions of different parts of the virus structure, and how these parts work together to cause disease.

What Is the Variola Virus?

Imagine a public health crisis. A highly contagious, disfiguring illness sweeps through your city. Patients don’t know they’re infected for up to 17 days. They have no symptoms, yet the virus multiplies inside of them, presenting an insidious threat to all those around them. Patients develop a high fever, flu-like symptoms, and characteristic pus-filled sores that kill 30% of those infected. Those fortunately enough to survive are disfigured for life.

Disfiguring sores are characteristic of infection with the variola virus

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This frightful scenario describes a smallpox outbreak in Boston in 1721 caused by the variola major virus. Today, smallpox has been eradicated due to vaccination efforts all over the world. In this lesson, we’re going to look at the structure and function of the agent that causes this horrific disease.


In order to understand how the variola virus causes disease, we first need to understand the structure of the virus, or the physical parts. The variola virus is large compared to other viruses, stretching 230 by 300nm.

For comparison, the rhino virus, or the common cold, is only 30nm in diameter. Consequently, the variola virus can nearly been seen under a light microscope, which is highly unusual for a virus.Scientists use the type of genome, or genetic material, the virus has to classify it. Variola virus has a double stranded DNA genome, meaning it has two strands of DNA twisted together, like our cells have.

The DNA is bound to proteins in a nucleoprotein complex called the core, shaped like a dumbbell in the center of the virus.

Electron micrograph of the variola virus
variola virus

The core is enclosed by a core membrane. The core membrane is made of lipids and proteins that protect the DNA, and other important proteins needed for the virus to replicate. A palisade layer made of protein protects the core, surrounding the core membrane.

Outside the palisade layer there are two lateral bodies. These areas contain important enzymes that the virus needs to replicate. Think of these areas as storage tanks. They store the enzymes until the virus is ready for them, and release them when they are needed.

The virus also has an envelope, an outer membrane made of host cell lipids. The envelope is made of three layers itself. First, there is an inner membrane, then an outer membrane and finally surface tubules, which help the virus attach to host cells.

Function and Replication

So, what’s the purpose of all these structures? What’s the virus’ end goal? The only goal of a virus is to reproduce. Although the virus causes disease, the main goal is to reproduce. The disease is a product of cell death and the immune system response. The virus wants to invade, hijack the host cell and make more of itself, sometimes killing the host cell in the process. Let’s look at how this happens during viral replication.

The first step in viral replication is when the variola virus enters the body. Droplets of liquid containing the variola virus from infected patients enter the respiratory tract through the mouth and nose. The variola virus attaches to respiratory endothelial cells, or cells that line your lungs.

The virus can also attach to cells in the immune system and cells that line your blood vessels. The virus also infects skin cells, which leads to the classic skin lesions seen in small pox patients.The virus attaches using the surface tubules, which bind to proteins on the outside of the host cells. When the virus attaches, the outer envelope fuses with the host cell membrane, releasing the core into the host cell’s cytoplasm. In the cytoplasm, lateral bodies release enzymes needed for the virus to start replication.

Replication of the variola virus

The virus now is able to hijack the host cell, taking it hostage. Variola tricks the host cell into making more copies of its DNA and proteins, which are needed to make more viruses.

The host cell doesn’t realize it’s making more viral parts, and unknowingly manufactures more and more virus particles. The host cell doesn’t just manufacture the parts, but assists in assembling the viruses also.The newly assembled viruses bud out of the host cell, grabbing some of the host cell membrane to form their outer envelope as they go. Not only does this add an extra layer of protection for the virus, but it camouflages it inside the body. The body sees its own membrane on the virus, which can slow the immune system from realizing there’s an intruder.

Lesson Summary

The variola virus is a large, double stranded DNA virus that is the causative agent of smallpox. The variola virus invades the respiratory system, skin, and blood vessels, leading to fever, and large pus-filled sores that can lead to disfigurement.

The genome of variola is enclosed in nucleoproteins in the core with two lateral bodies that contain enzymes to assist in replication. The core is covered in the core envelope, palisade layer, and finally an outer envelope, which is made of host cell membrane and surface tubules.The variola virus infects host cells by attaching to the surface and releasing the viral core into the cytoplasm. Lateral bodies release enzymes that are needed to hijack the host cell into making more viruses. New viruses bud out from the host cell, camouflaging them to infect other body cells and evade the immune system.

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