Exam 4 Flashcards
What is a Transformed Cell?
When a cell has new genetic material that changes its normal functions.
What are the 8 characteristics of a transformed cell?
- immortal: can grow indefinitely
- reduced requirement for serum growth factors
- loss of capacity for growth arrest upon nutrient deprivation
- growth to high saturation densities
- loss of contact inhibition (can grow over monolayers)
- altered morphology
- anchorage independence
- Tumorigenic
What is Acyclovir?
A highly effective anti=herpes simplex virus drug
What are the structures of acyclovir?
They are nucleoside analogs. Acyclic Sugar Group
How does acyclovir work?
Acyclovir compounds, ACV, is only phosphorylated by HSV thymidine kinase. Keeps adding additional phosphates which then get inserted into the virus genome by viral DNA pol. ACV does not have 3’ OH so replication is terminated.
What is immune memory?
The secondary response to a pathogen, after already seeing it, there is a stronger response in T cells and Antibodies. Immune system’s ability to recognize the return of a pathogen and respond quickly to it.
What is immune memory?
The secondary response to a pathogen, after already seeing it, there is a stronger response in T cells and Antibodies. Immune system’s ability to recognize the return of a pathogen and respond quickly to it.
Adenovirus
Strucutre, Genome, Attributes
Icosahedral T=25. Genome: dsDNA. Non enveloped. Cause cancer in hamsters, Viral T antigens are E1A and E1B which transforms cells. E1A necessary for E transcription units. Frees E2F. E2 is required for DNA synthesis and entry into L phase. IVa2 enhances L gene transcription.
What is Retinoblastoma, RB
Rb is a gene/protein that controls entry into the S phase (DNA replication) of the cell cycle. It is a tumor suppressor gene. Regulates restriction point of cell cycle.
What are T antigens?
They are virus encoded transcriptional regulators of both viral RNA and Host RNA. They are also responsible for transforming cells.
What do T antigens do?
Required for Replication
Activate viral transcription
Required for viral DNA synthesis
Only viral genes retained in tumor or transformed cells
can transform cultured cells alone
What are active vaccines?
A modified form of pathogen or a product derived from that pathogen that induces immunity. Provides long term protection.
Types of vaccines
Attenuated Vaccines
Inactivated vaccines
Frctionated Vaccines (subunits)
Cloning Vaccines
Transducing vs Non-Transducing Virus
When did viruses evolve and come to be?
Viruses came billions of years ago, predated cells. 450 million years ago were first estimated, herpesvirus arose 220 million years ago.
Why do viruses develop resistance to antivirals?
Viruses replicate efficiently to overcome constraints. Modest to high mutation frequencies.
Mechanism of drug resistance
Error prone RNA pol causes mutations and has no proofreading. DNA evolve more slowly than RNA viruses due to less diversity. RNA more prone to develop drug resistance.
Example of drug resistance
HSV develops drug resistance spontaneously. Causing some mutants not able to phsoporylate acv because of viral tk not working.. also sometimes they wont incorporate acv into DNA because DNA pol not working.
Examples of viruses that transform or cause cancer.
SV 40
Polyomaviruses
Papillomaviruses
Adenoviruses
How do viruses immortalize cells
They can deactivate tumor suppressor genes such as Rb and p53 that allow the normal cell cycle to continue indefinitely. SV40 LT sequesters p53. Adenovirus forms complex to ubiquitinated p53. Papillomavirus e6 binds to p53.
Stage of Mitosis
PPMAT.
Prophase - Centromeres begin to align, nucleus begins to degrade, Chromosomes begin to condense
Prometaphase - Nucleus completes degradation, chromosomes start to attach to spindle.
Metaphase - Chromosomes align in division plate.
Anaphase - Chromsomes are split into sister chromatids by centromeres, cell furrow begins to stretch.
Telophase = Actin wraps around furrow further separating the 2 sister cells.
What is a persistent infection?
Asymptomatic and Pathogenic. Aysmptomatic, virus continues for life but symptoms not apparent. Pathogenic, have long initial latent periods before fatal symptoms.
Occur when infection is not cleared by immune response. Viral genomes remain even if proteins are not in tact. No single mechanism.
Examples; EBV, HCV HBV, and Papillomavirus.
What is a subunit vaccine?
Vaccine that breaks virus into components, immunizations occurs with purified components. Antigen is usually a capsid or membrane protein. HBV vaccine is example. Gardasil and Cervarix
What is an attenuated vaccine
Live virus that is weakened. Infection induces mild or inapparent disease. Empiraccaly attenuated, grow the virus in nonhuman cells and wait for evolution to have the virus to specify for nonhuman type. Then innoculate weak viruses for humans to have an immune response.
What is an inactivated vaccine
Virus infectivity is eliminated, but antigenicity is not compromised. Undergo chemical procedures to deactivate such as formalin. Polio vaccine is example.
Normal Cell Cycle
G1 - Nomal metabolic Growth, prepping for DNA replication.
S - DNA replication and synthesis
G2- Second growth phase prepping for mitosis
M - Mitosis, then cytokinesis
How can cells be transformed by viurses?
The infected cell does not die.
Transformed cells do not produce virions
It becomes immortal
Effective Vaccines are:
Induce appropriate immune response; Th2 response wanted.
Antibodies are produced to provide protection from pathogens.
Safety: No disease, minimal side effects.
Induce protective immunity
Long-lasting protection.
Low cost, stable, and storage and delivery viable.
What are the 4 general patterns for infection?
Acute, Latent, Persistent - Asymptomatic, Persistent- Pathogenic
What are acute infections?
Example
Short duration, high viral titers, sometimes severe disease state. Rapid onset of viral reproduction.
Influenza, Poliovirus, Measles Virus, Norovirus, West Nile virus.
What are latent infections?
Similar to acute, followed by periods of inactivation and reactivation. Everthing is infected by a chronic latent infection.
Herpes simplex virus
Persistent - Asymptomatic
Virus production continues for life in the host, but symptoms are not apparent. Occur when virus is not cleared by immune system.
Adenovirus, ebv, JC virus
Persistent - Pathogenic
Such as HIV. follow no symptoms for long latent period but then cause severe fatal symptoms.
HIV, SSPE
Retrovirus history
Developed 450 mya
Costs of drug discovery
R&D- 10-100m$
Preclinical : 10mil
Phase 1: 10 mil
Phase 2: 10-100mil
PHase 3: 100mil
What is viral virulence
Capacity of a virus to cause diease in a host
Virulence can be quantified
Viral titer, Appearnce of signs and symptoms, fever/weight loss, measure of pathology, mortality.
Specific ways to measuring virulence
Measurement fo survival
Measurement of pathogenic lesions
LD50: Median Lethal Dose, number of infections particles will kill 50%
ID50: Median infectious dose. # of infections particles to infect 50% of challenged recepients.
What are restriction points?
Points in the cell cycle that pauses if conditions are not correct.
p53 pauses before s phase.
Cyclins CDK.
WHat is herd immunity?
When the spread of disease drops below a threshold. Population scale immunity. People are indirectly protected by vax individuals.
Papillomaviridae.
HPV viruses. Oncogenic. First DNA virus identified. Causes warts. But Viral T antigens by E6 and E7 cause immortalization.
What are 4 main drivers of viral evolution?
Large # of progeny
Large # of mutants
Quasi-Species effects
Selection
Large # of progeny
Allows for rapid evolution as selective pressures are more sensitive in populations that have fast replication cycles.
Large # of mutants
RNA viruses are more error-prone thus have more ability to produce mutant strains. With large progeny, mutations can appear quickly.
Quasi Species effect
Viruses don’t exist as exact copies in a population but have similar replicons. Sometimes they have a consensus sequence. But most genomes may not have one.
Selection
Survival of the fittest. Those that are able to successfully replicate, or develop beneficial mutations are more likely to have those mutations continue on.
Specific Mechanisms for evolution
Genetic bottlenecks. Co-evolution between host and pathogen.
What is metagenomics
Evaluation of all of the genomes in a community. All the genomes within the sample without the need to culture them. unbiased evaluation, and using bioinformatics to process data.
Why do we use matagenomics?
To study phylogentics, gind taxonomic diversity, and discover new viruses within the environment.
Find out which viruses are abundant.
