Module 11 - Viral Pathogenesis Flashcards
What is viral pathogenesis?
The mechanisms where viruses cause disease in target hosts
What must viruses do to reproduce?
- Get into permissive host
- Acquire resources needed for replication
- Evade host defenses
- Spread to new hosts
What feature of viruses makes pathogenesis more complicated compared to bacteria?
They must replicate intracellularly
For viruses, what is infection?
Entry of a virus into a host cell
What is a productive infection?
New infectious viral particles are produced (viral replication occurs)
Which cell leads to productive infection?
A permissive cell
What is an abortive infection?
Few, if any, new viral particles are produced (viral replication does not occur)
Which cell leads to abortive infection?
A non-permissive cell
What are the different types of viral infections?
Acute, latent, and persistent
What is an acute infection?
An infection with a short duration
What are some characteristics of an acute infection?
Signs/symptoms observed, infection is cleared, usually results in immunity
What is an example of an acute infection?
Rhinovirus infection (common cold)
What is a latent infection?
A period of acute infection is followed by latency
What causes an infection to be latent?
The virus is still present, but replication is shut down
What does reactivation mean in a latent infection?
Reactivation can lead to the recurrence of acute infection signs and symptoms
What are some examples of latent infections?
Lambda phages and herpesviruses
How do lambda phages remain latent?
Via repression by the cI repressor
How do herpesviruses remain latent?
Through LATs
What does LAT stand for?
Latency associated transcripts
What do herpesviruses maintain during latency?
A circular episome
What does HHV-1 lead to?
Cold sores and genital sores
What does HHV-2 lead to?
Cold sores and genital sores
What does HHV stand for?
Herpesvirus
What does HHV-3 lead to?
Chicken pox rash and shingles
What does HHV-4 lead to?
Burkitt lymphoma, mononucleosis
What does HHV-8 lead to?
Kaposi sarcoma lesions
What is another name for persistent infections?
Chronic infections
What is a persistent infection?
New viral particles are continuously produced
What are some characteristics of a persistent infection?
The host does not clear the virus, but signs and symptoms may cease
How come the host may not clear the virus in a persistent infection?
Either targeted weakening of the immune system, or mutational changes in the virus and/or host target cells
What are some examples of persistent infections?
Hepatitis B and C
True or false: hepatitis B and C are always persistent
False: they are not always persistent, but they can be in some individuals
What are the basic types of viral transmission?
Horizontal, vertical, zootonic, and mechanical
What is horizontal transmission?
Transfer from individual to individual within the same species
What does horizontal transmission require?
A mode of exit and mode of entry
When someone says they “caught” a cold from someone, what type of transmission is this?
Horizontal transmission
What are some examples of horizontal transmission?
Respiratory, fecal/oral, and sexual
What are some examples of respiratory horizontal transmission?
Rhinoviruses, influenza
What are some examples of fecal/oral horizontal transmission?
Polioviruses, hepatitis A
What are some examples of sexual horizontal transmission?
HIV, human papillomaviruses
What is vertical transmission?
Transmission within the same species, from mother to fetus or newborn
What are some mechanisms of vertical transmission?
Via placenta/during birth, via breast milk, or via germ cells
What are some examples of vertical transmission via placenta/during birth?
Rubella, hepatitis B and C, HIV
What are some examples of vertical transmission via breast milk?
HIV
What are some examples of vertical transmission via germ cells?
Spermatocytes/oocytes infected with mouse mammary tumor virus (MMTV)
What does MMTV stand for?
Mouse mammary tumor virus
Which vertical transmission is intensely studied?
HIV vertical transmission
How come rates of HIV vertical transmission have dropped in the US?
Antiretroviral drug therapies and C-sections
What is zootonic transmission?
Transfer between individuals of different species (from animals to humans)
What are some examples of zootonic transmission?
Rabies, West Nile, and Ebola
What may zootonic transmission lead to?
More widespread horizontal transmission events
What is an example of zootonic transmission leading to more widespread horizontal transmission events?
HIV arising from SIV
What is mechanical transmission?
Facilitated transfer of virus from host between individuals in the same species
How can viruses travel in mechanical transmission?
Via vectors like mosquitoes, or contaminated medical equipment
What are some examples of mechanical transmission?
Myxoma virus and yellow fever in mosquitoes, Ebola in contaminated medical equipment, plant viruses
What is viral exposure?
Simply coming into contact with a virus
When does an infectious disease occur?
During a productive infection
What do almost all viral infections activate?
The host immune system
What does the overall outcome of viral infection depend on?
The interplay between viral replication and immune response of the host
What type of infection is the majority of viral infections?
Acute infections
In acute infections, what does the severity of symptoms depend on?
The rate that the virus replicates, and the strength of the individual immune response
What are the best studied human viruses that exhibit latency?
Herpes viruses
What happens after acute infection of HSV-1?
It enters the nuclei of neurons
What happens after HSV-1 enters the nuclei of neurons?
It exists as an episome
What is an episome?
A non-integrated extra chromosomal closed circular DNA molecule that can be replicated in the nucleus
What genes are expressed in the HSV-1 episome?
LATs
What happens when HSV-1 is reactivated from latency?
The viral particles travel back down the neuron to the periphery to cause disease symptoms
How might a virus maintain a chronic infection?
By weakening the immune system, or suppressing apoptotic signals
True or false: Ebola virus can be transmitted in various ways
True: it has multiple mechanisms of transmission
Why do rhinoviruses cause sneezing and coughing?
They allow the virus to leave the infected individual and find a new host
How can Ebola virus be transmitted horizontally?
By direct contact with contaminated bodily fluids
Why might a virus only be transmitted zootonically and not horizontally?
The virus is dead in the human host, and thus cannot spread
How can rabies be transmitted to humans?
Through the saliva of an infected animal
How is Ebola transmitted zootonically to humans?
Either directly through bats, or indirectly from primates
What does SIV stand for?
Simian immunodeficient virus
What is HIV to SIV an example of?
A zootonic virus mutating to become more infectious to humans
How does the myxoma virus gets transmitted?
By rabbit to rabbit via mosquitos or fleas (mechanical transmission)
True or false: the myxoma virus replicates in the mosquitoes or fleas
False: they just act as passive vectors
True or false: yellow fever virus replicates in the insect vector
True: unlike myxoma virus, it can replicate in the insect vector
How can Ebola virus be transmitted mechanically?
Through medical devices contaminated with the blood of an infected individual
How do some viruses cause cytopathology?
By inhibiting host cell transcription and translation processes, or avoiding immune responses
How can viruses induce cellular damage?
Through necrosis, apoptosis, or inclusion body formation
Why might a virus induce necrosis or apoptosis?
It gives it access to more resources for translating its own proteins
How does poliovirus lead to necrosis?
It inhibits host cell mRNA translation
How does poliovirus inhibit host cell mRNA translation?
It cleaves an essential translation initiation factor (eIF-4G)
What happens when eIF-4G is cleaved by poliovirus?
Rapid inhibition of host cell translation, and initiates translation of viral mRNA
How does cleaved eIF-4G lead to translation of viral mRNA?
It is moved to internal ribosome entry segment of the viral mRNA to initiate translation
What does IRES stand for?
Internal ribosome entry site
What does an IRES do?
An RNA element that allows for translation in a cap-independent manner
What is needed for the initiation of the translation complex in eukaryotic cells?
A 5’ cap
How does bunyavirus lead to necrosis?
Through a cap snatching process
What happens when the cap is stolen from mRNA?
It is promptly degraded
Besides bunyaviruses, what other viruses cleave the 5’ cap off of mRNA?
Automyxo viruses
What do cap-snatching viruses do with the 5’ cap?
Use it to prime synthesis of viral mRNA
What is apoptosis?
Programmed cell death
What type of organisms undergo apoptosis?
Multicellular organisms
How does apoptosis work?
Biochemical processes lead to characteristic cell changes
What are some characteristic cell changes during apoptosis?
Blebbing, global mRNA decay, and chromosomal DNA fragmentation
When might induction of the apoptosis pathway be useful?
To prevent the production of more virus particles and limit the spread of virus within the host