Chapter 9, Problem 1CS

CASE STUDY |Zigs and zags of the smallpox virus

Smallpox, a once highly lethal contagious disease, has been eradicated worldwide. However, research continues with stored samples of variola, the smallpox virus, because it is a potential weapon in bioterrorism. Human cells protect themselves from the variola virus (and other viruses) by activating genes that encode protective proteins. It has recently been discovered that in response to variola, human cells create small transitory stretches of Z-DNA at sites that regulate these genes. The smallpox virus can bypass this cellular defense mechanism by specifically targeting the segments of Z-DNA and inhibiting the synthesis of the protective proteins. This discovery raises some interesting questions:

What is unique about Z-DNA that might make it a specific target during viral infection?

Summary Introduction

To review:

The uniqueness of the Z-DNA (deoxyribonucleic acid) that results in the targeting of these segments during a viral infection.

Introduction:

The variola virus is known to cause contagious disease smallpox in humans. The cells in the human body shows an immune response against the virus by activating genes, which encode for protective proteins. These proteins are known to be regulated by the segments of Z-DNA. Recent discoveries have been made regarding the capability of the variola virus to inhibit the synthesis of protective genes by targeting the Z-DNA segments.

Explanation of Solution

The Z-DNA is discovered by the Andrew Wang, Alexander Rich, and their colleagues in 1979 during the examination of a small synthetic DNA fragment, which contains only G ≡ C base pairs, having a left handed double helix configuration. The variola virus is a brick-shaped large virus that has double-stranded DNA that is linear. The virus has multiple infectious forms that are attained during a life cycle. The disease is spread by inhalation of airborne virus. The Z-DNA is an alternate form of DNA that has a left-handed helix with a diameter of 1.8 nm. There are 12 base pairs per turn. The Z-DNA forms zig-zag confirmation.

It was observed that the variola virus was unable to affect human cells because of the formation of protective proteins. These proteins were formed on the activation of the specific genes when the body was exposed to the virus. The cells of the human body create stretches of this alternate form of DNA on exposure to the virus. These stretches are introduced at the site where the genes can be regulated.

The unique helical arrangement of the Z-DNA provides an important site for recognition for interaction with other molecules. As the stretches of the DNA are formed on exposure to the virus, it is considered to play a role in the formation of protecting protein coded for fighting the infection. This might make Z-DNA the specific target during viral infections.

Conclusion

Thus, it can be concluded that the left-helical structure of the Z-DNA makes it a target site for the virus.