SPH PH 510 Lecture Notes - Lecture 17: Reassortment

Influenza viruses are an important cause of respiratory infection in humans and also infect other host species such as pigs and birds. The ongoing epidemic and pandemic threat of influenza virus infection to the human population is primarily caused by antigenic change and escape of the virus from immune mediated protection. Discuss the different mechanisms leading to these changes and provide an overview of the dynamics of infection and transmission between these different hosts.

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Class 6: Viruses (and Cells, continued)


Making connections: viruses and microbes Match the cell biology concept (on page 1) with an important application of that concept (on page 2). Then answer the follow-up questions at the bottom of page 2.


Cell Biology concepts
1. Bacteria that cannot construct new cell wall material become fragile and break down.
2. During influenza infection, the viral enzyme neuraminidase is required to release new viruses from the host cell in which they were made. Once released, the new viruses can infect many additional cells.
3. Thermus aquaticus is a bacterium found in hot springs and can live at temperatures up to ~80°C (175°F). It has adapted so that its enzymes are most functional at the elevated temperatures, compared with many organisms’ enzymes that function best ~37°C (98°F).
4. Until the isolation and investigation of retroviruses, scientists thought that RNA could be copied from DNA, but DNA could not be copied from RNA. Research on this class of viruses led to an update to this “Central Dogma” of biology.
5. Some bacteria have adapted, so that the enzymes involved in making cell wall materials have a slightly different shape and can no longer be bound by certain drugs.
6. Rhizobia are bacteria that colonize the roots of certain plants (legumes, including beans and peas). The host plant benefits from the prokaryotes’ ability to “fix” nitrogen, converting N2 from the atmosphere into a form that is usable by the plant.
7. Many species of bacteria contain the enzyme cellulase. More than 10 billion such bacteria and other symbiotic microbes may be found in a single milliliter of material from inside the digestive system of ruminant mammals.
8. Fungi, including those that cause athlete’s foot, use ergosterol to maintain healthy membranes. Animal cells do not make ergosterol, they use a similar lipid – cholesterol.
9. During retrovirus infection, a DNA copy is made of the virus’s RNA genome. A cut is made in the host cell’s DNA and the DNA copy of the viral genome is pasted into the host chromosome by a viral enzyme called integrase.
10. Prokaryotic cells contain smaller ribosomes (“70S” ribosomes) than eukaryotic cells (“80S” ribosomes). Both types of ribosomes synthesize proteins, but the macromolecules they use to do it are somewhat different.



2
Applications
_______ Oseltamivir, also called Tamiflu, binds and inhibits the viral protein neuraminidase.
_______ Clotrimazole is a drug that is used to treat certain infections. It interferes with synthesis of ergosterol, a lipid involved in phospholipid membranes.
_______ Penicillin is a drug that interferes with synthesis of peptidoglycans (these are biological molecules that are part protein and part carbohydrate) that are present in certain cell walls.
_______ HIV is often treated with several drugs that inhibit different parts of the viral replicative cycle. Raltegravir is an example of a drug that interferes with the integration of viral genes into the host cell’s chromosome.
_______ Cows, like other vertebrates, lack the ability to breakdown cellulose. Yet they are able to live on a diet of grass and other vegetation high in cellulose.
_______ Enzymes isolated from extremophiles have been very useful in laboratory research. For example, Taq polymerase facilitates PCR, a revolutionary technique for production of DNAs of particular sequences, which requires cycling reactions through high temperatures.
_______ Plants and animals require nitrogen to make biological macromolecules, however they’re unable to convert atmospheric nitrogen (N2) into a biologically useful form.
_______ Azithromycin is a drug that binds to 70S ribosomes and blocks synthesis of any new proteins.
_______ Methicillin-Resistant Staphylococcus aureus (MRSA) can cause life-threatening infections of the skin and bloodstream. One of the reasons MRSA infections are so serious is that they are resistant to treatment by many antibiotics, including methicillin and penicillin.
_______ The enzyme reverse transcriptase, isolated from retroviruses, is an important tool in molecular biology research. Scientists interested in learning what genes are turned on in particular cells use it to make DNA copies of RNAs they are studying (The DNA copies are useful because they are more stable).

When you have completed the matching activity, answer these follow-up questions:
• What types of infections can be treated with the following drugs?
o Penicillin
o Clotrimazole
o Azithromycin
o Tamiflu
o Raltegravir
• Why are these drugs (above) safe for you to take? That is, why don’t they kill your cells?
• Cancer cells are your own human cells that have become deregulated so that they divide and pile up in an uncontrolled way. Many chemotherapy drugs treat cancer by interfering with cell division and other cell processes.
o Why are there so many more side effects for individuals undergoing chemotherapy than for individuals taking antibiotics?

1. Unlike Ebola virus, SARS virus
a. has large spikes that look like a “crown”.
b. is enveloped.
c. is helical.
d. is in the family Togaviridae.
e. is a ssRNA virus.

2. Which virus or virus family is described in the followingpassage?
Electron micrographs of the hemagglutinin subunits (in the presenceof SDS) showed
rods approximately 40 Ã wide and 140 Ã long. The neuraminidasesubunits had a quite
different appearance. In the presence of SDS, these were seen asoblong structures about 85 Ã long and 50 Ã wide with a centrallyattached fibre 100 Ã long possessing what appeared to be a diffusetail or small knob about 40 Ã in diameter at its end.1
a. Togaviridae
b. Epstein-Barr virus
c. Smallpox virus
d. Orthomyxoviridae
e. Filoviridae
f. Rabies virus

3-Following is a passage from the New England Journal ofMedicine:
______________________ is an exclusively human herpesvirus that ...becomes latent in
cranial-nerve and dorsal-root ganglia, and frequently reactivatesdecades later to produce shingles and postherpetic neuralgia. Inimmunocompetent elderly persons or
immunocompromised patients, ____________________ may producedisease of the central nervous system.
This passage refers to which virus?
a. West Nile virus
b. Smallpox virus
c. Epstein-Barr virus
d. Ebola virus
e. Varicella-zoster virus

4. Pneumoviruses can cause colds and pneumonia in humans. They aresingle-stranded,
negative-sense, nonsegmented RNA viruses. These enveloped virusesare surrounded by an envelope that is characterized by fusionglycoproteins and host-derived proteins. With this knowledge, it islikely that pneumoviruses
a. enter host cells via endocytosis.
b. leave host cells by budding.
c. enter host cells via membrane fusion.
d. A and B
e. B and C

5. Recall that poliovirus is a positive-sense (+) ssRNA virus. The5’ à ? 3’ strand of RNA,
once uncoating has taken place, can serve as an mRNA and encode forviral proteins.
However, in order for the virus to create more +ssRNA to package indaughter viruses, it must
a. generate a dsRNA molecule that can encode for the synthesis ofmore +RNA.
b. integrate into the host cell DNA.
c. utilize an RNA-dependent DNA polymerase to make aheteroduplex.
d. undergo reassortment
e. All of the above

6. Some influenza hosts, such as humans and pigs, cansimultaneously contract human,
avian and swine influenza viruses at the same time. What can occurduring the maturation phase of virus replication in such ahost?
a. Reassortment
b. RNA of all three sources: human, swine and avian, can bepackaged into a single
virion.
c. Genetic shift
d. All of the above

7. The HIV virion contains enzymes/proteins that do all of thefollowing EXCEPT
a. An enzyme that creates –DNA using +RNA as template.
b. A protein that serves as a chemokine receptor.
c. A DNA-dependent DNA polymerase.
d. An enzyme that allows +/- viral DNA to be spliced into the hostcell’s DNA.
e. A protein that mediates membrane fusion.

8. After a long series of biochemical tests, Kyle and Matt werefinally able to identify their Gram-negative unknowns asPseudomonas aeruginosa and Shigella dysenteriae,
respectively. As they compare notes, they realize that theirunknowns are in the
___________ Pseudomonadaceae and Enterobacteriaceae, respectively.However, they also note that both of their unknowns are in the______________ ? proteobacteria.
a. genera, species
b. phyla, family
c. families, class
d. order, phyla
e. classes, order

9-Hydrogenobaculum acidophilum is a resident of Yellowstone’sNorris Geyser basin. This thermoacidophilic microbe grows instringy, white mats and is a member of the phylum Aquificae.Hydrogenobaculum acidophilum
a. could be further researched in Volume 2 of Bergey’s Manual ofSystematic
Bacteriology.
b. is in the domain Archaea.
c. is a deeply branching bacterium.
d. is a proteobacterium.
e. All of the above

10-After talking about the Group A Streptococci (GAS) and theircapability to sometimes cause a flesh-eating disease callednecrotizing fasciitis, Derek decides to research this group a bitmore. As he reads, he quickly learns that
a. they are microaerophilic Gram-negative rods.
b. they are in the phylum ?-proteobacteria.
c. they are found Volume 4 of Bergey’s Manual of SystematicBacteriology.
d. they have less than 50 mol % GC content.
e. none of the above