1. Mutations can have one of all of LESSON 4.5 WORKBOOK the following effects EXCEPT: aa 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 bb The mutation may produce a virus that is defective in some way. As discussed in the last lesson, mutations are cc 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 dd 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. ______3. A mutation may be favorable to the virus. ______Even though we are talking about viruses here it Figure 1: A mutation in a gene may ______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 aa swapping viral genes; random mutations that accumulate during replication mutation bb swapping genomes; random As we saw in the last lesson, mutations in viral mutation genomes, either DNA or RNA, can accumulate quickly cc random mutation; swapping because viruses often lack proofreading enzymes. genomes This is why there is a high likelihood that new virus dd 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 aa True mucosa of the lower respiratory tract is thought to be why H5N1 is more deadly than H1N1. bb 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 new virus needs 4. In an antigenic shift, the resulting to have a certain number and type of segments genome will contain to be functional. In this case that will be one large (in aa only the parent genome. grey), one middle (green or yellow), and one small bb genomes not present from (blue or red) gene segment. But the new viruses parent genomes. assemble with a random combination of these cc genomes from both parent segments, possibly generating a new type of virus genomes. with genes from both parent viruses. This is depicted in Fig. 5: the resulting new viruses have segments dd all of the above from both parent genomes — the new viruses have ______swapped their middle size segments, green and ______Figure 5: Segmented viruses can yellow, creating progeny viruses that are very differ- exchange genes when they infect the ent from the parent types. To top that, they will also ______same host cell. So the offspring of have any mutations they acquired by antigenic drift ______segmented viruses can contain genes during replication! ______from both parent viruses plus differ by ______antigenic drift. Will this swapping cause change in function? Prob- ______ably. For example, the new viruses may acquire a ______new collection of entry receptors allowing them to infect a whole new set of cells — think back to H1N1 ______and H5N1. H1N1 could quite conceivably acquire new entry receptors from H5N1 through antigenic ______shift when both viruses infected the same cell. Keep in mind that the depicted swapping is not the only ______possible one in reality the combinations are practically infinite. ______Workbook ______Lesson 4.5 ______179 STUDENT RESPONSES

H1N1 and H5N2 can undergo antigenic shift. The H and N genes are on independent gene segments. What variants of influenza could you get? Will the new viruses be more or less virulent?

______Remember to identify your ______sources ______

Construct an explanation based on evidence for why adaptation does not occur in the absence of natural selection.

______Workbook ______Lesson 4.5 ______180 TERMS

TERM DEFINITION

Antigenic Having the ability to be recognized by the immune system as foreign, and provoke the production of antibodies.

Gene A particular sequence of DNA or RNA that contains information for the synthesis of a protein or RNA molecule.

Segmented genome A genome that is fragmented into multiple pieces instead of contained in one large molecule.

Viral strain Genetic variant of the same virus.

Workbook Lesson 4.5 181