Virus overview
What are viruses? What is their Genome? How do they act?
Viruses are not organisms they are particles or agents; and they are obligate(inherently negative) parasites. Viral genomes can be either DNA or RNA and can be double stranded(ds) or single stranded(ss). Viruses enter a host cell and take over its biosynthetic machinery- and since they are not alive- they depend solely on host cell machinery.
What are the two types of viral lifecycles?
Lytic and Lysogenic.
What is the current “novel coronavirus“ named?
what is the name referring to the human disease state?
5pt. Bonus: Where does the strain of coronavirus that affects humans originate from?
Name(s): SARS-CoV-2 or SARS-2.
Name referring to human disease state is COVID-19.
Bats.
What sense type(+) or (-) and strand type is the SARS-2 genome?
what does this sense type do and what happens?
SARS-2 genome is comprised of (+) single stranded RNA.
The “+” genome refers to RNA strand that contains the open reading frame for proteins like mRNA.
The viral +RNA genome is immediately translated upon entry into the cytoplasm, and ends with viral proteins being produced.
short answer: “+” strand mRNAs are used to translate viral proteins and to be the genomes of new viral particles using “stolen” endomembrane envelopes to package.
1.What are the two ways a person can get active immunization?
2. What is an antigen?
3. What do antibodies and T cells do to antigens?
1. Can be acquired naturally contracting a disease or can be acquired artificially via vaccines.
2. An antigen is a part of a pathogen(typically a protein or carb) that is recognized in the immune system. An antigen can come from either an infection or a vaccine.
3. Once a pathogen is recognizable, antibodies and T cells will fight the pathogen with this antigen.
What is the difference between (+) and(-) stranded DNA/RNA.
Positive-sense (+) genome strands act directly as mRNA, allowing immediate translation into proteins by host machinery upon infection, while negative-sense (-) strands are complementary to mRNA, requiring transcription into a positive strand by viral enzymes before protein production can begin.
List the characteristics of the lytic lifecycle. What types of cells does the lytic lifecycle infect?
5pt. bonus, Name a disease affected by lytic lifecycles.
During the lytic lifecycle: The viral genome enters the host cell and its genes gets transcribed and translated and then the viral genome is replicated. Once the virus is released it kills the host cell and spreads by infecting other cells or other hosts.
The lytic lifecycle occurs in epithelial cells and when released viruses infect sensory neurons.
Ex. of a disease with this lifecycle is Herpes outbreak
List the components(e.g.structural, genomes etc.) of COVID-19.
*COVID-19’a genome is made up of ssRNA.
*( The virus has a membrane envelope(from the human host cell).
*has a spike glycoprotein that allows the virus entry into human cells.
What needs to happen to the viral genome if it is ssRNA for further genomic copies to be made? What is the name of this product and, what is turning the ssRNA into the product?
what does the product do?
Since the genome is ssRNA, it needs to be copied into a NEGATIVE(-) complementary strand by the viral RNA-dependent-RNA-polymerase protein(RdRp). This negative strand RNA is used as a template to synthesize many more viral ”+” strand RNAs.
What is an attenuated/replicating vaccine? List its characteristics.
15 pt. bonus: What is a way to create a weak pathogen?
20pts bonus: What are the risks you run if you give an attenuated vaccine to someone who is immunodeficient?
An attenuated vaccine has a weakened, live version of the pathogen in it. This type of vaccine establishes Transient infection upon vaccination, which boosts and lengthens the immune response, and the immune system is exposed to all pathogen antigens in it; but needs a live pathogen.
A way to create a weak pathogen is to culture it in non-human host cells. This allows the pathogen to adapt through mutation to the non-human host and thus loses the ability to effectively grow in a human host.
1. patient cannot fight off infection, even though virus is weakend.
2.Virus might re-adapt to be effective in humans and then infect other people.
How have many viruses evolved due to their compactness?
Evolved due to the overlapping of reading frames: when two proteins are encoded by a segment of DNA read in different reading frames.
List the characteristics of the lysogenic lifecycle. What types of cells does the lysogenic lifecycle infect?
5pt. bonus, Name a disease affected by lysogenic lifecycles.
Lysogenic viral gemone INSERTS itself into host genome(lytic does not), and replicates its genome as the host cell divides. In non-dividing cells, some lysogenic viruses package their genomes into heterochromatins without genome insertion. This lifecycle has a period of quiescence, and viral sequences in each cell can later be reactivated to produce viral particles.
Lysogenic lifecylce occurs in neuronal cells, reactivation happens when the neuron makes a few viral particles(and survives).
A disease operating with a lysogenic lifecycle is HIV.
State the components that make up the spike protein.
Overall what do these components do?
Spike protein has:
*RBD: area that binds to the human ACE2 receptor.
*Furin cleavage site: sequence recognized by a human protease.
TM: Transmembrane domain.
these regions provide the “engine“ for membrane fusion and viral entry.
what do viral proteins use for translation?
Host cell rinosomes.
What is an inactivated vaccine? List its characteristics.
20pts. What are some pros and cons to this vaccine?
An inactivated vaccine is a dead version of the pathogen, that is killed by heat(denaturation) or formaldehyde(cross-linking). Inactivated vaccines don't case infection and only expose the immune system to some pathogens.
Pros: Readily incorporated into other vaccines(1 injection many diseases), contains multiple pathogenic proteins, easy to ship & store, and no reversion to virulence.
Cons: lower immune response, immune system only exposed to surface proteins
List correlations between Viral genomes and Evolution. List the ways evolution happens to viruses at its pace.
Evolution acts on DNA variation to select organisms that have higher fitness compared to their competitors leading to changes in genomes over time. For viruses this selection goes very fast for reasons like:
*Viruses compete in large numbers, so even a tiny advantage can win out.
*Viruses make more mistakes than other organisms during replication leading to much more DNA variation.
*Viruses have rapid replication time(hours)leading to many generations per time.
* Viral genomes are in a shell(protein or membrane), so size impacts fitness, smaller = more fit.
What are Retroviruses? What are the two key enzymes they depend on? What do these two enzymes do?
Retroviruses are RNA viruses(ex. HIV). They depend on the enzymes Reverse Transcriptase and Integrase. Reverse Transcriptase copies RNA genome into dsDNA. Integrase inserts virus DNA into genome.
What is ACE2? What does it do? Where is it typically found?
10pt. Bonus is SARS-2 infection of cells with ACE-2 lytic or lysogenic? How do you know?
ACE2 is a human protein that normally helps regulate blood pressure. And is found on the cell surface of a subset of airway epithelial cells.
Lytic, lytic lifecycle occurs in epithelial cells.
Which cells can SAR-2 infect?
a). Any human cell
b.) any human epithelial cell
c). any human lung epithelial cell
d). Any human cell expressing ACE2?
D.
What is a Purified Protein vaccine? List its characteristics.
20pts. What are some pros and cons to this vaccine?
A Purified Protein vaccine is the synthesis of either all or part of a pathogenic protein in a lab, not a pathogen.
Pros: Do not have to culture a pathogen, depending on the protein, can be set up quickly, no virulence
Cons & Challenges: Protein must fold in the lab the same way it folds in humans, protein may have complicated post-translational modifications that have to be replicated in the lab, Immune system only exposed to 1 pathogenic protein, viruses can evolve resistance through missense mutations. int he one targeted protein leading to anitbodies no longer matching.
What do Proteases do?
Proteases cut the long polypeptide into small individual proteins allowing multiple proteins to be encoded by a single open reading frame.
Why are lysogenic viral infections nearly impossible to "cure" e.g. HIV infection of T cells?
This is because the viral genome is inserted into the host's T cells, not its own separate cells. Additionally, Lysogenic viruses can be latently infected meaning it is inactivated and the immune system cannot recognize the cell as being infected. Once the cells reactivate- there are already too many infected cells for the immune system to combat.
How does SARS-2 infect humans, including:
Defining endocytosis.
5pt. Bonus what makes SARS-2 not infectious to humans?
SARS-2 spike protein binds to human cells that express the ACE2 protein. This binding triggers viral endocytosis(active transport process that is receptor mediator and is when the pathogen or other eukaryotic materials are engulfed and wrapped by a plasma membrane, to then be pinched off into an internal vesicle). Once the Furin cleave site is cleaves by a human protease, releasing the “head group” and allows the fusion machinery to function efficiently. *without Furin cleavage site, SARS-2 is NOT infectious in humans. Once virus fuses its membrane with the endocytic membrane, the viral genome is released into the cytoplasm.
What do DNA viruses use to replicate their genome? 5pts. Name a DNA viral genome diseas.
What do RNA retroviruses use and do to replicate their genomes? 5pts. Name a retrovirus disease.
DNA viruses use DNA polymerase to replicate their genomes. Ex. Herpes.
RNA retroviruses use reverse transcriptase to reverse transcribe RNA to DNA, then use host DNA polymerase to replicate and host RNA polymerase to transcribe their genomes. Ex. HIV
What is a mRNA vaccine? List its characteristics.
mRNA vaccines are similar to purified protein vaccines as they both use one pathogenic protein, but in mRNA, instead of synthesizing the protein in a lab, the injected mRNA encodes the pathogenic protein.
The mRNA is coated in delivery lipids that can fuse with human cells, human cells take up the mRNA & synthesize the proteins.