Viruses. Are Viruses Living Things? Introduction and Importance. Structure

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1 Are Viruses Living Things? Viruses Do you remember the properties of life from Biology 1100? Viruses can t propel themselves, can t grow, can t break down organic matter and store its energy, and don t have a cellular structure. Some don t even have any DNA. Most biologists in the past have thought that viruses are not alive. On the other hand, viruses do have a complex internal organization, they base their heredity on nucleic acids, they can sense signals from the environment and react to them, and they certainly can evolve. Some biologists conclude that they are alive. Therefore, we will start these diversity modules with a brief overview of viruses, viroids, and prions. The emphasis will be on viruses of humans. By the way, the Latin word virus means poison. Introduction and Importance Viruses are essentially complex molecular assemblages. They always have either DNA or RNA (but usually not both) enclosed in a protein shell called a capsid. The only way they can reproduce is by infecting a host cell and hijacking its machinery to make new viruses. Viruses cannot be cultured in a cell-free medium, and they cannot break down organic matter and store its energy. On the other hand, they can be crystalized and stored on a shelf as if they were a big molecule like a protein. Despite these simple characteristics, viruses are enormously important. We are most familiar with their role in disease. Viruses cause colds, flu, herpes, smallpox, chickenpox, measles, mumps, encephalitis, many respiratory and intestinal infections, hepatitis, warts, yellow fever, dengue fever, hemorrhagic fevers like ebola, some pneumonias, AIDS, and even some kinds of cancer. Most humans have from 2-6 viral infections per year. Viruses also cause many animal and plant diseases. We are also beginning to realize that viruses are important in the environment as well. After many years of believing that viruses were very rare in the oceans, now we think that 70% of marine prokaryotes may be infected by viruses, and these viruses might cause a large part of marine bacterial mortality. Some researchers say that over 50% of the biomass of the oceans may be viruses. Finally, viruses may be important in evolution. When viruses lyse bacterial cells, they increase the amount of free DNA that can be taken up and used by other cells. Sometimes viruses also transfer genes directly to bacteria and even to humans. For example, the spread of antibiotic resistance is probably speeded up by viruses that transfer resistant DNA between bacteria. As another example, in 2006 it was found that cyanobacteria (blue-green algae) have a great diversity of photosynthetic genes, probably because these genes were transferred between species by viruses that infect the cyanobacteria. Perhaps viruses that transfer especially effective genes are favored when their host cyanobacteria can capture more solar energy and reproduce faster. Structure First, viruses are very small, even by microscopic standards. If a red blood cell is the size of a frisbee and a spherical bacterium is about the size of a golf ball, the largest virus would be about the size of a marble, and the smallest would be about the size of a grain of sand. That is, viruses range in diameter from about 300 nm down to 20 nm. The usual diameter of a bacterial cell is about 1,000 nm. Of course, you remember that a micrometer has 1,000 nm. As explained above, a virus always has a core composed of either DNA or RNA. Only cytomegalovirus and a large DNA virus called a Mimivirus have both. Of course, all cells do have both of these nucleic acids.

2 This leads to one of the important ways by which viruses are classified--into DNA viruses and RNA viruses. Furthermore, the viral nucleic acid could be either single-stranded (ss) or double-stranded (ds). This leads to four large groups of viruses: ssdna ssrna dsdna dsrna The most common arrangement is dsdna, and most RNA viruses tend to be ssrna. Further distinctions are made based on whether a single RNA strand is directly useable as mrna (ssrna +), or whether it is complementary to the mrna that must be made (ssrna -). Compared to cells, viruses only have a small amount of nucleic acid. A human cell has about 6 billion base pairs (bp) of chromosomal DNA and a bacterial cell has about 4 million bp, but a large DNA virus may only have about 200,000 bp, and a small virus may have less than 5,000 bp. This may only be enough to code for 3-4 proteins. At the other extreme, Mimivirus has about 1 million bp, larger than the genomes of some bacteria. The capsids of viruses tend to be geometrical. Two common shapes are cylindrical (also called helical or spiral), and icosahedral (a solid figure consisting of 20 triangular sides). Sometimes a "helical" virus is not just a simple cylinder; the helical virus that causes an African hemorrhagic fever called ebola has a twisted cylinder. Some viruses have complex shapes, which are combinations of the icosahedral and helical virus shapes. The familiar T4 bacteriophage is an example. Capsids tend to use many repeats of the same protein (a capsomere), in the same way that a house may consist of many identical bricks. This saves on the genetic information that is needed to encode the capsomeres. The elongated, purple objects in this diagram are the individual capsomeres. Finally, many viruses, especially animal viruses, have an envelope outside the capsid. This is composed of host cell membrane, but with viral proteins protruding through it to form spikes. These spikes often allow the virus to lock onto molecules on the surface of the host cells. Life Cycle Viruses cause disease because of their parasitic lifestyle. While a viral infection could kill a cell in less than half an hour, a more sophisticated viral infection could go on for decades with almost no ill effects. The simplest viral life cycle is the lytic cycle, which is very straightforward and destructive. The virus locks onto the cell surface and either injects its DNA or RNA inside the cell or gets it inside in some other way. The nucleic acid makes copies of itself and later of the capsid proteins using the cell s ribosomes and enzymes. Eventually, the cell lyses and releases hundreds or thousands of viruses. Or perhaps, less dramatically, new viruses bud from the membrane of the host cell. These viruses infect other cells. We ll now look at each of these steps in detail. Finding an appropriate host cell is vital, and relies on receptors on the viral surface that connect with cell surface molecules. This is why spikes are so important in enveloped viruses--a virus without spikes would be unable to find a host cell. Measles virus can infect most human tissues because it locks onto very common molecules, but polio virus can only lock into tissues in the nasal passages, gut, and nervous system. After locking onto a host cell, the virus or its nucleic acid must get inside. Sometimes this is done by injection of the DNA or RNA from the outside, and sometimes the whole virus is taken inside (common in animal cells). Some viruses can trick the cell into actively taking them in by endocytosis. If the whole virus is taken in, then the nucleic acids must be released from it.

3 Nucleic acid replication comes next. In some cases, the virus has no enzymes of its own and relies on host polymerases. In other cases, it may bring in enzymes (e.g., reverse transcriptase) to help with this step. Viral DNA is commonly made in the nucleus and viral RNA is mostly made in the cytoplasm. Manufacture of the capsid proteins is done by hijacked host cell ribosomes. The capsomeres selfassemble because they are more stable as a capsid than as individual proteins. The viral DNA or RNA then gets inside by an unknown method. This is sometimes very tightly packed--a certain virus that infects bacteria has 500 µm of DNA wound into a space no more than 0.1 µm across. This is akin to packing half a kilometer of thread into a baseball without getting the thread hopelessly tangled! In 2008, it was found that in one virus this packing is done by a molecular motor powered by the host cell s ATP. Finally, the new viruses must exit from the cell. In a naked (without an envelope) virus, this is usually by cell lysis. In this case, the virus final act as a resident in the cell is to cause the manufacture of enzymes that degrade the cell membrane and/or wall. The cell lyses and the viruses escape. In many enveloped animal viruses, however, the virus seeds an area of membrane with spikes, and then buds through the membrane, taking the spiked area of membrane with it as an envelope. This quiet shedding of viruses can go on for some time before the cell dies. Not all viral infections have lytic cycles that result in release of new viruses. Many viruses have a lysogenic cycle in which viral DNA inserts itself into host chromosomes and remains as a silent provirus, perhaps for many years. Then, some stimulus, perhaps stress, causes the DNA to exit the chromosome and start replicating. In some bacterial viruses (bacteriophages), the virus DNA remains lysogenic and reproduces with the cell as long as the cell is growing and dividing. However, if the host cell s survival seems in doubt, the virus becomes lytic and escapes. As an analogy, if a ship is in good shape, it doesn t make any sense to leave it. However, if the ship is sinking, it s time to get in a lifeboat and row away. Why Viruses Make Us Sick Viruses cause pathology for a variety of reasons, although sometimes it s not clear why they cause the symptoms they do. First, obviously, lysing of cells is going to cause pathology for the host. This pathology will be worse if the lysed cells can t be replaced (e.g., polio virus infecting the nervous system) than if they can be replaced (nasal cells lysed by the cold virus). Viruses can have other bad effects on cells as well. They can inhibit DNA and protein synthesis and can cause lysosomal rupture. The seeding of cell membranes with large numbers of viral spikes can disrupt membrane function. Some viral proteins are directly toxic to cells. Insertion of viral DNA in chromosomes can disrupt the chromosomes. Finally, a few viruses can cause cells to become malignant (cancerous). Treatment of viral illness is difficult. If a bacterium is making us sick, we can take an antibiotic that works against prokaryotic metabolism. However, the metabolic machinery being used by viruses is all our own. If a drug inhibits it, it will probably hurt us as well. One thing that every aspiring doctor should remember is that antibiotics are useless against viral infections. Prescribing antibiotics for colds and flu doesn t inhibit viruses but does encourage the development of antibiotic-resistant bacteria. Classification Viruses are not given binomial names, but they are classified into groups (based on their kind of nucleic acid), families, genera, and species. For example, one kind of smallpox virus is in Group I

4 (dsdna), family Poxviridae, the subfamily Chorodopoxvirinae, the genus Orthopoxvirus, and species variola major virus. You will see the most references to virus families. We will now review these general principles with three viral examples--a T4 bacteriophage, influenza virus, and HIV. T4 Bacteriophage T4 is a virus of bacteria (a bacteriophage, pronounced bak-teer-ee-oh-fayj ). T4 bacteriophage is a naked virus with dsdna, and belong to the family Myoviridae. One of its startling features is that this virus that never infects eukaryotes has introns in its DNA! A T4 phage lands on a bacterium by locking onto surface lipopolysaccharides or proteins. Within 2 minutes, it has lowered itself to inject its DNA into the bacterium. By 3 minutes, the host DNA is degraded and the bacterial cell s metabolic machinery is totally hijacked for making phage particles. By 5 minutes, the phage DNA is being made; by 12 minutes, capsid proteins are being assembled into capsids; by 22 minutes the cell lyses and releases about 300 new phage particles. T4 only has this lytic life cycle--it cannot become lysogenic. Before antibiotics, bacteriophages were deliberately given to patients in the hopes that they would lyse pathogenic bacteria! This therapy was especially common in the Soviet Union. Giving patients viruses to kill bacteria sounds crazy, but it worked, and it s being considered again today for antibioticresistant bacteria. Remember CRISPR/Cas9? This molecular biology method can cut DNA almost anywhere, depending on directions contained in a guide RNA (grna). CRISPR/Cas9 evolved as a bacterial defense against bacteriophages like T4. The guide RNAs that direct it are complementary to bacteriophage DNAs that have infected that lineage of bacteria in the past. You may remember that restriction enzymes also originated as bacterial defenses against bacteriophages. Influenza Virus A The common flu virus is ssrna (-), meaning that its hereditary material is single-stranded RNA that is complementary to (rather than identical to) the messenger RNA it will need to make. It is an enveloped animal virus of the family Orthomyxoviridae. Because of its envelope, the influenza virus looks like a sphere with spikes protruding through its membrane. The two main spike materials are hemagglutinin (H) and neuraminidase (N). Flu strains are named after these. For example, bird flu stain H5N1 has hemagglutinin type 5 and neuraminidase type 1. The great Spanish flu epidemic of was caused by strain H1N1. Influenza virus enters a cell by receptor-mediated endocytosis, the RNA is released and +RNA is made from the -RNA in the virus. This +RNA then serves as a template for the making of numerous copies of -RNA. Meanwhile, other +RNA serves as mrna and makes viral capsid and spike proteins. The virus has genes for 10 different proteins. Rather than lysing the cell, the virus seeds an area of plasma membrane with spikes and then buds from that area, taking the membrane and spikes with it. The pathology of influenza is probably caused by the death of respiratory epithelial cells. This is caused by the immune response to the virus, not the virus itself. Flu keeps flaring up year after year because in certain areas of the world, especially in rural China, domestic birds like chickens and ducks transmit new virus strains to pigs. Here they combine with human viruses, and then a genetically new human flu strain is transmitted every year from pigs to

5 humans. Flu epidemics tend to originate in East Asia, reach Europe and North America in 6-9 months, and then die out when they reach South America several months after that. If you think flu epidemics are just an annoyance, think of the Spanish flu of It killed million people, 2.5-5% of the human population at the time. It has been observed that AIDS killed 25 million in 25 years, but the Spanish flu killed 25 million in its first 25 weeks. My mother, who was four years old in 1918, had vivid memories of hiding in a closet and tearfully praying that her parents would not catch the deadly influenza. HIV-1 Human immunodeficiency virus (HIV), the cause of acquired immune deficiency syndrome (AIDS), is designated as ssrna (RT), meaning it is a single-stranded RNA virus of the family Retroviridae. Being a retrovirus means HIV uses RNA as a template to make DNA. Note that an ordinary RNA virus like an influenza virus does not do this--the flu virus makes RNA from RNA, not DNA from RNA. HIV has an envelope, and looks like a sphere with 72 spikes. These spikes are the object of intense research because they allow the virus to infect cells of the human immune system. The virus has a coneshaped capsid inside the envelope. This contains its two molecules of RNA plus three enzymes. Infected semen, vaginal secretions, or blood carry the virus to several different kinds of immune cells (which we will cover when we do the immune system), and the virus is taken inside the cells. The enzyme reverse transcriptase takes a +RNA strand and makes a DNA-RNA hybrid strand. Then it degrades the RNA strand and makes a complementary DNA strand, resulting in dsdna. Finally, this dsdna integrates itself into the host chromosome, forming a provirus. The proviral DNA in the host cell chromosome may remain quiet for years, or it may start making viral RNA and proteins, causing the shedding of viruses. The shedding disrupts membrane function. Immune cells rely on their membranes to recognize pathogens and respond to chemical signals, so this depresses the immune response. After a period of infection, it also kills the immune cells. Over about 8-10 years, the immune system fails, the victim develops full-blown AIDS, and dies from opportunistic infections, cancer, or degeneration of the nervous system. The mean survival time after full-blown AIDS develops is only 9 months. While it has nothing to do with the virus, the following table on the probability of becoming HIV+ from one episode with an HIV+ person is interesting. Activity Probability blood transfusion childbirth sharing needle receiving anal intercourse penile-vaginal intercourse (woman) giving anal intercourse penile-vaginal intercourse (man) Attempts to produce an anti-hiv vaccine have been unsuccessful because the virus changes its surface proteins so fast. This fast mutation is a characteristic of retroviruses because their reverse transcriptase makes many errors as it converts RNA to DNA. So if the virus had more precise reproduction, it might have been controlled long ago. It is thought that HIV originated when SIV (simian immunodeficiency virus) crossed from chimpanzees to humans sometime in the 1930s in the African country of Cameroon. The first known HIV+ blood sample was taken from a man in central Africa in The disease was first recognized in 1981, and by 2004, 26 million people had died from it. This makes it one of the great epidemics of history.

6 Viral Evolution Viral evolution is a mystery. We can identify birds and mammals as different groups, and we rightly expect that bird DNA will be most similar to other bird DNA, and mammal DNA will be most similar to other mammal DNA. However, viral DNA and RNA is usually more similar to the DNA/RNA of the host it infects rather than to the DNA/RNA of other viruses. This implies that viruses originated independently many times and are not related to each other. In other words, while we believe there was a single ancestral cell, there probably was no single ancestral virus. The accepted theory on how viruses originated says that they came after cells, and resulted when DNA and RNA released from cells became coated with protein and became infective. According to this theory, viruses are derived from cells, and are not in any way representative of pre-cellular life. An alternative theory centers on a very large DNA virus called a Mimivirus, that infects amoebae. This virus has such a large genome that some researchers suggest that it evolved from a more complex ancestor, perhaps free-living and cellular. The theory says that this ancestor then lost functions and became an obligate parasite in cells. This story was supported with the 2013 discovery of another kind of large virus, the "Pandoravirus." This virus looks like a cell (although it is definitely a virus), is the size of a bacterium (1.2 µm long) and has a genome of 2.5 million base pairs, as large as the genome of a bacterium, and as large as the smaller genomes of the eukaryotes. So, some viruses may have originated from simplified cellular life, and may have existed early in the history of life. Of course, it might be true that some modern viruses originated from nucleic acids released from cells, and some might be simplified cells. We may never know how viruses evolved, but it is clear that they are an important component of our world today. Satellites, Viroids, and Prions These three infective entities are collectively called subviral agents. Viroids are small molecules of naked ssrna (without protein) that reproduce in plant cells and cause about 16 plant diseases. Remember that the smallest viruses have 5,000 nucleotides--viroids have only nucleotides. Satellites are like viroids except that they consist of either DNA or RNA and cannot reproduce in a cell unless the cell is already infected by a certain virus. The satellite uses the replication machinery of the virus. Prions are proteins (without any nucleic acids) that cause several nervous system diseases of humans and animals, including mad cow disease. It is thought that a prion somehow causes misfolding of proteins, which causes still other proteins to misfold.

7 Biology 1110 Virus Worksheet 1. Why have biologists traditionally concluded that viruses are not alive? 2. What was the module's capsule description of a virus and its lifestyle? 3. Name some common human diseases caused by viruses. 4. Why do we say that viruses have an important role in evolution? An important ecological role? 5. A typical human cell is a cube 10 µm on a side. How many large viruses could be laid along one edge of this cell? How many of the small viruses? Yes, you'll need a calculator. 6. Consideration of nucleic acids allows us to divide viruses into four major types. What are these types? 7. What is a capsid? What are the two most common capsid shapes? Why are capsids often composed of many identical proteins? 8. What is a viral envelope? A spike? Why must enveloped viruses have spikes? 9. Distinguish between a lytic viral life cycle and a lysogenic viral life cycle. 10. Why can some viruses only infect certain species, and certain cells within that species? 11. Which part of a virus must get inside the host cell if an infection is to be started?

8 12. Can a virus manufacture proteins by itself? How are capsid proteins made? 13. Contrast the methods used by naked and enveloped viruses for exiting from host cells. 14. Name three ways in which viruses make us sick. 15. Drugs against viruses are as primitive today as drugs against bacteria were in the 1930s. Why are safe and effective antiviral drugs so difficult to produce? 16. What is a bacteriophage? Describe the steps in the lytic cycle of a T4 phage. 17. CRISPR/Cas9 and restriction enzymes originated as bacterial defenses against bacteriophages. Explain how these defenses worked. What did they do to defeat the phages? 18. What does it mean to say that the influenza A virus is "ssrna (-)"? Does this virus ever make DNA from RNA? 19. Describe how an influenza virus exits from a host cell. 20. The swine flu that caused such anxiety in 2009 was strain H1N1. What do these letters and numbers mean? 21. If you had measles, you probably only had it once because your immune system is prepared to fight off the infection it ever reappears. Why can you get flu again and again? What do ducks and pigs in China have to do with this explanation?

9 22. HIV is a "retrovirus." What does this mean? How is a retrovirus different from other RNA viruses? What is the importance of reverse transcriptase for a retrovirus? 23. Some people are exposed to HIV and develop AIDS rapidly, but others go on for years without symptoms. Why the difference? 24. Why does HIV have such a devastating effect on the immune system? 25. Why can't we produce a vaccine against HIV? 26. "Viral taxonomy is not phylogenetic." What does this mean, and why do we believe that it is true? 27. According to the conventional theory, how did viruses originate? Why do the Mimiviruses and Pandoraviruses suggest an alternative theory of viral origin? 28. Distinguish between a virus and a viroid. Between a virus and a prion. Between a viroid and a satellite.

10 Biology 1110 Viruses 1. The word virus means 1. invisible. 2. mystery. 3. destroyer. 4. poison. 2. Many biologists would claim that viruses are not alive. While we might argue over whether they are sufficiently complex or how they reproduce, everyone agrees that no virus 1. can grow. 2. can break down organic matter and release its energy. 3. has a cellular structure. 4. All of these. 3. Viruses generally have 1. either DNA or RNA (but not both) inside a protein shell. 2. many contractile filaments made of actin. 3. ribosomes made of rrna only (rather than rrna and protein). 4. All of these. 4. Most viruses range in size from... µm. Note the unit used. Yes, you may have to convert some units , You would expect that most of the protein in a virus would be found in its 1. chromosome. 2. capsid. 3. nucleosome. 4. membranes. 6. All cells have heredity based on double-stranded DNA, and all cells use single-stranded RNA in protein synthesis. What about viruses? 1. Some viruses have heredity based on either single- or double-stranded RNA. 2. Some viruses use double-stranded DNA as their hereditary material. 3. All viruses use RNA in protein synthesis. 4. All of these. 7. If an RNA is virus is "+," this means that its RNA 1. can be used directly as mrna. 2. is read 5' to 3' rather than 3' to 5'. 3. has both deoxyribose sugar and uracil. 4. uses the same genetic code as cellular life. 8. A certain virus is said to be a "naked icosahedron." The outer surface of this virus would look like 1. a spindle shape composed of nucleic acid wound around histone proteins. 2. a hazy layer of glycoproteins overlying a membrane thrown into many microvilli. 3. an angular, geometric shape made of proteins. 4. a more-or-less spherical shape made of a plasma membrane studded with many protruding proteins. 9. Another virus is said to be an "enveloped icosahedron." The outer surface of this virus would look like 1. a spindle shape composed of nucleic acid wound around histone proteins. 2. a hazy layer of glycoproteins overlying a membrane thrown into many microvilli. 3. an angular, geometric shape made of proteins. 4. a more-or-less spherical shape made of a plasma membrane studded with many protruding proteins. 10. Viruses have many different life cycles, but all viruses must get their... inside the host cell. 1. capsid 2. nucleic acid 3. capsomeres 4. at least one spike

11 11. Viruses have both lytic and lysogenic life cycles. You would expect to see... only in the... life cycle. 1. formation of a provirus... lysogenic 2. transport of viral nucleic acid into the host cell... lytic 3. self-assembly of capsids from capsomeres... lysogenic 4. replication of the virus DNA along with the host DNA... lytic. 12. Viruses make eukaryotes sick in several ways, but not by 1. triggering cancer. 2. converting chromosomal DNA to RNA. 3. lysing cells. 4. disrupting membrane function with spikes. 13. It is much harder to design drugs to cure viral infections than to cure bacterial infections because viruses, in contrast to bacteria, 1. are not alive, and therefore cannot be killed. 2. use proteins (such as reverse transcriptase) that are not found in any cell. 3. use the host's own metabolic pathways. 4. do not break down organic matter and release its energy. 14. The T4 bacteriophage 1. injects DNA through its "tail." 2. only has a lytic life cycle. 3. uses host ribosomes to make its proteins. 4. All of these. 15. The influenza virus uses its "spikes" to 1. rip the cell membrane when it lyses the host cell. 2. recognize an appropriate host cell. 3. cut up hydrolytic enzymes that are attacking the virus. 4. hold antibodies away from the virus so they do not bind to it. 16. HIV is called a retrovirus because it 1. makes DNA from its RNA hereditary material. 2. makes mrna from proteins. 3. injects protein as well as nucleic acid into its host cell. 4. escapes from host cells by budding rather than by lysing. 17. Taxonomy of cellular organisms attempts to be phylogenetic. Most discussions of virus taxonomy start by saying that it is not phylogenetic. We think this because viruses 1. are not subjected to natural selection because they are not alive. 2. have no independent existence because they can't live without their host cells. 3. that look alike have very different DNA and/or RNA. 4. have no genes in common with the cells they infect. 18. A prion is like a virus because it...; it is unlike a virus because it 1. integrates itself into the chromosomes of host cells... can multiply outside of its host cell. 2. has single-stranded DNA... never uses RNA. 3. has a capsid and a nucleic acid... injects protein rather than nucleic acid into the host cell. 4. is a molecular entity that multiplies in a host and causes disease... does not have any nucleic acid.

12 Biology 1110 Viruses Correct. Poison or venom. All disease agents, even bacteria, were sometimes called viruses in the 1800s Correct. Viruses never increase their size, never break down food molecules (they use energy stored in ATP of their host cell), and they certainly aren't cellular Correct. 2. No. A few bacteriophages have tail filaments, but I don't believe they're actin. 3. No! No virus has a ribosome. Viruses use only host cell ribosomes Correct nm = µm. All the other answers have an upper range that's way too large and 3. No. Viruses don't have chromosomes, certainly not chromosomes with protein or nucleosomes. 2. Correct. 4. Some (enveloped) viruses do have membranes, but most of the protein would not be in the membrane Correct. Some viruses also use ssdna Correct. Its RNA is identical to the mrna it must make. 2 and 3 are never true, and 4 is true of all viruses, so that can't be why some are designated "+." No. A naked virus would not have a membrane or a glycocalyx. 3. Correct. It would be a solid geometric figure assembled from numerous capsomeres. 4. No. The roughly spherical shape is correct, but you were told the virus was naked Correct. The polyhedral shape of the naked capsid would be softened and rounded by the plasma membrane of the envelope. The protruding proteins are the spikes of the envelope Correct. A virus must get DNA or RNA into the host cell. Many leave their capsids and spikes on the outside when they enter Correct. The provirus is viral DNA or viral-made DNA that integrates into the host chromosome in the lysogenic life cycle. 2. No. This would happen in both the lytic and lysogenic life cycles. 3. No...only in the lytic cycle. 4. No...this is more likely in the lysogenic cycle Correct. Some viruses destroy host DNA, but they don't convert it to RNA No, while this might be philosophically true, it is not the reason drug design is difficult. 3. Correct. If a drug inhibits the virus, it will probably inhibit our own cells Correct. T4 does all these things Correct. They are receptors for host cell surface molecules Correct. This is backwards ("retro") from the way it usually works Correct. 1 and 4 are not true, and 2 is irrelevant Correct. A prion is protein alone. It "multiplies" by causing misfolding of existing host proteins, not by actually making copies of itself the way a virus does.