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Bio 102 Practice Problems Viruses Multiple choice: Unless otherwise directed, circle the one best answer: 1. A naked virus would probably get its DNA into a human cell by: A. B. C. D. E. Budding Endocytosis Active transport Injection Diffusion 2. The types of cells that can be infected by a particular virus is primarily determined by A. what type of nucleic acid makes up the viral genome. B. the presence of specific molecules in the cell wall. C. whether or not the cell is actively dividing or if it’s in G0. D. what cells have the receptor. E. whether or not the virus has an envelope. 3. Enveloped viruses enter their host cell using A. endocytosis. B. budding. C. pinocytosis. D. lysis. E. exocytosis. Short answer (show your work or thinking to get partial credit): 1. You are a member of a scientific debate team. The topic is: "Are viruses living?" a. You have been given the "pro" side--what specific evidence can you present to support the idea that viruses are very simple living organisms? (1) Viruses have genetic material (2) Viruses use the same genetic code as all organisms (3) Viruses have the same basic components (nucleic acid, protein, lipids if enveloped) as other living organisms (4) Viruses can reproduce themselves (under appropriate conditions) (5) Viruses can infect cells, potentially cause disease and spread (6) Some viruses carry enzymes such as polymerases b. Now imagine you have been given the "con" side--what specific evidence can you present to support the idea that viruses are not living? (1) Viruses do not have membranes that function in transport, etc. (2) Viruses cannot replicate independently--they must use the machinery of a living cell (3) Viruses have no metabolism of their own (4) Viruses have no functional enzymes when they are outside a cell (5) Viruses have no energy-generating system (6) Viruses are much smaller than even the simplest cells (7) Viruses have no ribosomes or other organelles 2. Many animal viruses are surrounded by a phospholipid bilayer, called the envelope. Why do we refer to this as an “envelope” and not a “membrane”? A cell’s membrane is not just a phospholipid bilayer: it’s a complex mosaic of lipids and proteins with many functions, including transport, communication, etc. The proteins in an enveloped virus’ bilayer are not functioning or involved in metabolism: the only major function of the envelope is to allow fusion with a new host cell. 3. Rotavirus, a common cause of gastrointestinal illness and sometimes life-threatening illness in children, is a small, naked virus with a double-stranded RNA (dsRNA) genome. Suppose you work for a pharmaceutical company that would like to develop an antiviral drug that could be effective in treating rotavirus-infected patients. So far, researchers at the company have come up with the following six drugs, all of which are effective in stopping the virus in laboratory cultures. For each drug listed, write Yes under “Useful in Humans” if the drug has the potential to be effective in treating actual patients, and No if it does not. Then briefly justify your choice. Useful in humans? Reason 1) Stops virus protein synthesis by binding ribosome No Virus uses human ribosomes; has none of its own (not selectively toxic) 2) Blocks synthesis of membranes No Naked virus, no envelope; no virus makes its own membrane, so this would also not be selectively toxic 3) Binds tightly to virus surface proteins Yes Could bind the protein that needs to interact with a cellular receptor and block virus from infecting cells 4) Binds tightly to a cell-surface protein that can act as receptor Yes Could keep the virus from binding and infecting the cell (could also inhibit an important cell function) 5) Specifically binds and destroys dsRNA Yes No dsRNA in a normal cell, so any of this that is present is viral 6) Blocks processing of viral proteins in the ER and Golgi No No way to specifically block viral proteins; would inhibit all cellular processing: not selectively toxic Effect of drug 4. You work for a drug company that would like to produce a drug to treat infection with the West Nile virus. Four possible molecules have been tested, and their effects on the virus are listed below. For each of these molecules, briefly tell how promising it would be as a therapeutic drug for use in humans. Then circle the letter of the one that you think would be the best candidate for further development. Molecule A: inhibits translation of viral mRNA. Not useful! Viral mRNA is translated by host (human) ribosomes, tRNAs, etc., so anything that could inhibit viral translation will also inhibit the host cell’s translation! Molecule B: blocks attachment by binding tightly to the spike proteins in the virus envelope. Very promising! A virus can only infect a cell if it can attach to a receptor, and for an enveloped virus such as West Nile Virus, the spike proteins are the means of attachment. A drug that could bind the spike proteins could stop the virus from infecting any more cells. Human cells don’t have the spike proteins, so assuming the drug is very specific, it has real potential. Molecule C: blocks attachment by binding tightly to the receptor protein in the cell membrane. Also potentially promising. This would work much like molecule B, except that it’s binding to the receptor on the cell, rather than the virus. The main drawback would be that the “virus receptor” on the surface of the cell presumably isn’t there just to allow viruses to bind—it almost certainly has some normal cellular function, so it’s possible that the drug would also block some needed process. Molecule D: disrupts the lipid bilayer making up the virus envelope. Not useful! The membranes of all of our cells are made up of the same kind of lipid bilayer that makes up a virus envelope—in fact, the virus envelope is “stolen” cell membrane! So this drug would disrupt host cell membranes and would probably be fatal. 5. Viruses are found throughout the living world; specific viruses can infect animals, plants, fungi and even bacteria. a. What two components are shared by all viruses? What kind of molecule is each of these components made of? 1) Capsid, made of protein 2) Genome, made of nucleic acid (DNA or RNA) b. What third component is sometimes found in animal viruses? What kind of molecule is it made of? Envelope, a phospholipid bilayer 6. Suppose you are a research scientist at a pharmaceutical company. Your company would like to produce antiviral drugs, knowing there would be a fantastic market for these products. You ask your staff to prepare proposals for drugs they would be interested in developing further. For each of the three proposals below, state whether this drug is a promising possibility or a dud, and explain your reasoning. a. A drug that inhibits viral replication by blocking protein synthesis. In preliminary experiments, this drug completely blocked production of new SARS viruses in cultured cells. Dud! Viruses use the host cells’ protein synthesis machinery! Sure, this stops the virus, but it will also kill the host cell. Not useful as a human antiviral drug. b. A drug that stops HIV from attaching to its cellular receptor. The receptor in this case is a protein on white blood cells that normally binds other white blood cells and stimulates an immune response to invading microbes. The drug binds tightly to the receptor so that the HIV virus can’t bind, and preliminary experiments show it reduces the ability of HIV to infect the cells by nearly 100%. Probably also a dud. While the idea of blocking HIV attachment is a good one, binding to this receptor could prevent the white blood cells from carrying out their normal immune function. However, it might be somewhat promising, because HIV patients already have problems with immune function; if the drug eliminated the HIV infection in a short time, the immune system could go back to normal once therapy was stopped. c. A drug that stops the herpes virus from uncoating. This molecule binds to the capsid proteins of the herpes virus and prevents the nucleic acid from being released. Preliminary experiments suggest it is about 95% effective in its current form. This is a promising possibility: the capsid proteins would be unique to the virus, and uncoating is essential for virus replication. Stopping the herpes virus specifically at this stage could be a good way to attack the infection. 7. Influenza (flu) viruses infect cells by first binding to a receptor using a viral protein called hemagglutinin (HA). “Bird flu” is currently a major news item because the virus that causes it has a high fatality rate for birds. The virus appears to be quite dangerous for humans, who can catch it by handling infected birds. However, the virus is not transmitted to or between humans easily because it can only bind a receptor found deep in the lung, not the usual flu virus receptor found in the upper respiratory system. What do you think would have to happen in order for the “bird flu” virus to be easily transmitted from person-to-person and cause a major human flu epidemic? A mutation in the gene for the hemagglutinin protein could change the shape of that protein so that it can bind to a different receptor. If a mutation allowed HA to bind the upper-resipiratory receptor, the virus might be able to spread easily from person to person and start a major epidemic (assuming the mutated virus still had a high ability to cause disease). 8. Your roommate doesn’t want to have any pets, because she’s concerned about the danger of catching potentially dangerous viruses from other animals. Can you reduce her concern by explaining how viruses work? Viruses can infect a particular cell only if a protein on the capsid (naked virus) or envelope (enveloped virus) can interact with a receptor on the cell. We’re different enough from most other animals that our cells won’t have the appropriate receptors for most of their viruses (though there are a few exceptions). 9. Why is it more difficult to develop effective anti-viral drugs compared to anti-bacterial drugs? All drugs are designed to be more toxic to the pathogen (virus or bacteria) than they are to the human host. In most cases, a small molecule that can inhibt an enzyme acts as the drug. Since bacteria have thousands of enzymes that are very different from their human hosts (prokaryotic vs. eukaryotic!), there are a number of different possible target enzymes. However, viruses encode very few enzymes. Instead they rely on human enzymes to make more copies of themselves and we can’t inhibit the human enzymes without killing the patient! True or False? Read carefully: a question is false unless it is completely true! T □ ■ ■ □ T □ ■ T F 1. There are presently no drugs that can inhibit viral replication F 2. Enveloped virues can be considered simple cells because they have membranes; naked viruses are not cells because they consist only of protein and nucleic acid F 3. A naked virus consists only of a nucleic-acid genome in a protein shell (capsid); an enveloped virus also has a membrane to allow for transport, signaling, and other functions. Matching: 1. We decided in class that whether you want to think of viruses as living or not, they certainly don’t qualify as cells. Fill in the following table to compare viruses to cells by placing a V in the box to identify a characteristic of viruses only, a C in the box to identify a characteristic of cells only, and a B in the box to identify a characteristic of both cells and viruses. B Have genes V Genetic material can be RNA C Surrounded by a fully functional membrane B Capable of some form of reproduction C Contain transcription and translation machinery B Composed of macromolecules, including proteins