1. Mutations can have one of all of LESSON 4.5 WORKBOOK the following effects EXCEPT: a. The mutation may have no How do viruses adapt — Antigenic effect on the virus’s ability to survive or become virulent. shift and drift and the flu pandemic b. The mutation may produce a virus that is defective in some way. As discussed in the last lesson, mutations are c. The mutation can create a DEFINITIONS OF TERMS made randomly. If you take a test and randomly virus that is more virulent. fill in the answers, do you think you will get them d. none of the above all right? No, but if you repeat your random ______________________________ Gene — a particular sequence answering thousands of times you might, and this ______________________________ of DNA or RNA that contains ______________________________ information for the synthesis of is how mutations work. Many mutations are silent a protien or RNA molecule. or harmful to the pathogen but the few that are ______________________________ helpful make the wait worth the waste. ______________________________ ______________________________ For a complete list of defined ______________________________ terms, see the Glossary. ______________________________ In this lesson we will further explore how viruses change and adapt. In particular, this lesson describes ______________________________ how the processes of antigenic drift (random mutation), and antigenic shift (swapping viral genes) lead to ______________________________ adaptations that keep viruses one step ahead of the immune system. ______________________________ ______________________________ Mutations in viruses can have one of three ______________________________ outcomes: ______________________________ ______________________________ 1. A mutation may have no effect on the virus ______________________________ structure and function. ______________________________ ______________________________ 2. A mutation may be unfavorable to the virus. ______________________________ A mutation may be favorable to the virus. 3. ______________________________ ______________________________ A mutation in a gene may Even though we are talking about viruses here it Figure 1: ______________________________ not affect a protein (left panel) or can is important to note that mutations also happen lead to changes in a protein (right panel) ______________________________ Workbook in the bacterial and parasitic pathogens we have that may be favorable or unfavorable. ______________________________ Lesson 4.5 discussed. This is an important process contribut- ______________________________ ing to drug resistance and immune evasion! 176 LESSON READINGS Viruses mutate via antigenic drift and antigenic shift 2. Antigenic shift is to ____ as antigenic drift is to ____. Antigenic drift is the name given to the random a. swapping viral genes; random mutations that accumulate during replication mutation b. swapping genomes; random As we saw in the last lesson, mutations in viral mutation genomes, either DNA or RNA, can accumulate quickly c. random mutation; swapping because viruses often lack proofreading enzymes. genomes This is why there is a high likelihood that new virus d. random mutation; swapping DEFINITIONS OF TERMS particles will have genomes coding for altered proteins. Such changes, may be detrimental or beneficial to the viral genes virus. For example, if the mutation leads to a change ______________________________ ______________________________ Antigenic — having the ability in the entry receptor protein of the virus, and it no Figure 2: Comparison of antigenic drift and shift: minor vs. major changes. ______________________________ to be recognized by the immune longer binds to the host cell, oops, that virus is dead. However, if a mutation leads to change in a protein on ______________________________ system as foreign, and provoke ______________________________ the production of antibodies. the surface of the virus, it may make it unrecognizable to the host immune system, even if the host was exposed to a different version of the virus in the past. ______________________________ ______________________________ Segmented genome — a In fact, this is how viruses replicate successfully in a host — they randomly guess on the test and then repeat this process enough times to ensure that one of them gets a perfect score. ______________________________ genome that is fragmented into ______________________________ multiple pieces instead of con- ______________________________ tained in one large molecule. We have all felt the consequences of this process; antigenic drift is the major reason why we need a new flu vaccine every year. The flu virus is an RNA virus, and as we learned in lesson 4.4, RNA viruses can’t ______________________________ proofread when copying their genomes. For this reason, RNA viruses are prone to high levels of muta- ______________________________ tions via antigenic drift. Hence, every year ______________________________ For a complete list of defined ______________________________ terms, see the Glossary. when the flu comes back around, it has drifted away from its previous form. ______________________________ ______________________________ Antigenic shift or how one virus can ______________________________ exchange genes with another ______________________________ ______________________________ Unlike the process of accumulating single ______________________________ mutations through antigenic drift, anti- ______________________________ genic shifts are much larger changes in the ______________________________ genome, and hence viral properties, that ______________________________ happen suddenly. However, only viruses with ______________________________ Workbook Figure 3: Two strains of the same flu virus ______________________________ infect different cells in the respiratory tract. segmented genomes, like influenza, can do Lesson 4.5 this. ______________________________ 177 LESSON READINGS As shown in the above picture, the influenza viral strain, H1N1, generally infects the mucosa of the upper 3. Antigenic shift allows one virus respiratory tract, whereas a different strain, H5N1 (also known as bird flu), infects the mucosa of the lower to exchange genes with another respiratory tract. Infecting the lower respiratory tract causes a severe immune reaction, leading to the virus. accumulation of fluid in the lungs, causing severe symptoms mimicking drowning. This ability to infect the a. True mucosa of the lower respiratory tract is thought to be why H5N1 is more deadly than H1N1. b. False ______________________________ On the other hand, the inability to infect the upper respiratory tract makes it harder for H5N1 to spread ______________________________ from person to person. But what if H1N1 and H5N1 could trade genes via antigenic shift? This could ______________________________ potentially make a virus that infects both the upper and lower respiratory tracts. This is why many scien- DEFINITIONS OF TERMS ______________________________ tists fear the flu over all other pathogens! ______________________________ ______________________________ Viruses with nonsegmented genomes can’t undergo antigenic shift Viral strain — genetic variant of ______________________________ ______________________________ the same virus. Now, let's answer the question: why viruses with ______________________________ nonsegmented genomes cannot undergo antigenic ______________________________ shift? In figure 4, the tan shape in the middle repre- ______________________________ sents a host cell. Each blue pentagon depicts a virus. For a complete list of defined ______________________________ The blue, yellow, red and green stars on the blue terms, see the Glossary. ______________________________ pentagons represent viral surface proteins or recep- ______________________________ tors. The colored lines within each virus represent the ______________________________ viral genomes. Here, the genomes are in one piece, ______________________________ hence nonsegmented, and each color represents a ______________________________ different gene within the genome. ______________________________ ______________________________ In this case, when a host cell is infected by two ______________________________ strains of a viruses (A and B) at the same time, the Figure 4: Nonsegmented viruses can't ______________________________ genomes of both viruses will replicate in the cell. exchange genes even when they infect the same host cell. ______________________________ When the new viruses are assembled, each virus will ______________________________ have a genome identical to one of the parent viruses ______________________________ with the exception of any mutations that occurred by ______________________________ antigenic drift during replication. ______________________________ ______________________________ Viruses with segmented genomes can exchange genes by antigenic shift ______________________________ ______________________________ Now, let's see how segmented genomes can undergo antigenic shift. In figure 5, the shapes represent ______________________________ Workbook the same structures as above. This time though, the two viruses (C and D) have segmented genomes: _____________________________ Lesson 4.5 composed of multiple pieces. When a host cell is infected with viruses C and D at the same time, the genomes of both viruses will replicate in the cell, but when the new viruses start to assemble the gene 178 LESSON READINGS segments can get mixed up. Each