Virology Flashcards
1
Q
What is the most abundant life form in the human body?
A
Bacteriophages
2
Q
What percent of our DNA is retrovirally infected?
A
8% and it accumulated through evolutionary time
3
Q
What kind of diseases do viruses cause?
A
- Acute (ex. cold)
- Persistent (hepatic and herpes)
- Recurrent (herpes)
4
Q
Largest virus
A
Pox Virus (and more recently minivirus)
5
Q
DNA virus v. RNA virus
A
We call it a “DNA virus” if there is DNA in the virion
We call it an “RNA virus” if there is RNA in the virion
6
Q
How do viruses replicate?
A
Viruses replicate by de novo assembly of preformed components. virus cannot do anything on itself. They go into the cell, and tell the cell make more viruses.
So every one cell can make hundreds or thousands new viruses, there is no doubling, no mitotic events, simply a factory.
7
Q
Attributes of Viruses
A
1) they are obligate intracellular parasites
2) They can influence behavior (sneezing or coughing) in order to spread but they have no means of locomotion, metabolism, or energy alone
8
Q
Discovering viruses of Ancient Times
A
With the help of DNA sequencing, we can go back and look at mummies and determine what viruses they may have had (i.e. Hep B in mummies thought to have smallpox)
9
Q
Viral diseases described in ancient sources
A
Rabies Measles Smallpox Polio Yellow fever
Not until the description of DNA and RNA as the genetic material of life has the true nature of viruses become understood.
10
Q
New Polio-like virus killing and paralyzing children
A
Acute Flaccid Myelitis, AFM
11
Q
Biggest Concern for destroying us all
A
Flu or flu like virus because respiratory infections are the best way to rapidly spread something
(ex. measles)
12
Q
Ways of Classifying Viruses
A
- Phylogeny
- Host Range
- Disease caused
- Tissues infected
- Capsid structure
- Presence or Absence of lipid envelope
- Viral genome (RNA or DNA)
- Segmented or non-segmented
- single or double stranded
- (+) sense or (-) sense
13
Q
Where does a virus replicate its genome?
A
Either in the nucleus or the cytoplasm
RNA VIRUSES MAINLY REPLICATE IN THE CYTOPLASM
14
Q
What protects the genome of a virus?
A
a protein coat called a CAPSID
15
Q
Define Envelope
A
A lipid bilayer surrounding the capsid
16
Q
Naked Virus
A
A virus with no envelope but do have a capsid.
Most naked viruses emerge from cells by cell lysis (bursting of the cell and kill the cell on its way out)
17
Q
Where does the envelope in viruses come from?
A
They acquire a cell derived lipid bilayer by emerging from the cell via budding or from intracellular membranes.
18
Q
Envelope Glycoproteins
A
transmembrane glycosylated proteins extending from the envelope which mediate attachment and entry of enveloped viruses into cells.
They are major determinants of cell tropism.
Envelope protein are major viral antigens.
They are usually trimers
19
Q
Nucleocapsid
A
The capsid + the viral genome. Both naked and enveloped viruses have this
20
Q
Enveloped viruses are sensitive to what?
A
- Detergents
- Heat
- Drying
- Bleach
21
Q
Naked viruses are resistant to what?
A
- Detergents
- Heat
- Drying
- pH
- Proteases
22
Q
Icosahedral
A
most animal viruses have an icosahedral capsid
best way to maximize internal volume with minimal number of similar subunits
20 faces - equilateral triangles
12 vertices - with 5 fold symmetry
Pentons make up the vertices
Hexons make up the sides
23
Q
Helical
A
Human helical viruses all have RNA genomes
e.g. influenza virus
24
Q
Complex
A
Pox viruses - helical structure plus some other structures that are not understood.
25
Self-Assembly
When a critical concentration of viral components is reached at the proper location in the cell, these parts self assemble into viral subunits and then into whole viruses as it is a naturally energy efficient shape
26
Five Basic Structural Forms of Animal Viruses
1) Naked Icosahedral
2) Enveloped Icosahedral
3) Naked Helical
4) Enveloped Helical
5) Complex Viruses
27
Bacteriophage Structure
Icosahedral head, helical body which act like a syringe, they inject their nucleic acid into the cell, and they get this feet that look like space ship.
28
Viral Replication, or the infectious cycle
From one virus binding to a cell to the production of new infectious viruses
Early:
Adsorption - binding to cell - the host range of the virus is often controlled here
Penetration - enters cell
Uncoating - releases viral genome within cell
Migration of genome to nucleus (many viruses, not all)
Late:
Replication of viral nucleic acid - replication of genome (DNA or RNA) Can happen in the cytoplasm or the nucleus, depending on the virus.
Transcription from genome yielding mRNA
Translation of mRNA to produce viral proteins
Assembly - virions constructed from viral proteins and nucleic acids
can happen in the nucleus or the cytoplasm, or a combination of the two
Release of virions - via budding or cell lysis
Spread to new host - transmission of virus to new cell or to new individual
29
Antigenic Sites
determine serology; antibodies NEUTRALIZE virus
30
Structure of Env Gylcoprotein
Typically made up of a transmembrane domain & an ectodomain (an outer/ outside the virus domain). It is the ectodomain that does the binding to the cell. And, it is the transmembrane that often mediates the fusion with the target cell.
31
Enveloped Virus Entry/Fusion
Fusion can happen at the cell surface (e.g. HIV) or the virus can first enter the cell in an endosome, then fuse with the membrane of the endosome to release the genome into the cell (e.g. influenza virus)
32
Naked Virus Entry
1) They use spikes and bind similar to envelopes and form endosomes (like adenoviuses)
2) they form endosomes on the outside of the cell. they won’t split open the endosome and deliver everything into the cytosol. In the case of poliovirus: they squirt their genome through the endosome into the cytoplasm. This is a way of helping to keep the cell from forming an intracellular immune response.
3) instead of delivering the genome into the cytosol, in this example it is delivering the genome right through the nuclear envelope; where it actually cracks open the endosome & in this case it also entering the nucleus.
33
Viral Replication
First of the "late stage" events
Viruses must replicate their genomes using either a
cellular polymerase or a viral polymerase, or both. It must also make mRNA to generate proteins and new virions.
34
Replicase
A viral nucleic acid polymerase
35
What makes a good drug target for viruses?
When a virus uses its own enzyme to do something
36
What makes a bad drug target for viruses?
When a virus uses a cellular enzyme since it is needed by the cell to do its normal functions and inhibiting a cellular enzyme can be toxic
37
the flow of genetic information is in one direction
dsDNA → mRNA (single (+) strand) → Protein
| transcription in nucleus and translation in cytoplasm
38
DNA-dependent DNA/RNA polymermase
uses DNA as a template to create either more DNA (replicate dsDNA) or to generate mRNA which is found in all cells
ex. RNA polymerase II
39
RNA-dependent RNA polymerase
use RNA as a template to generate RNA, or to generate DNA*
| If a virus wants to use RNA as a template it must make its own enzyme.
40
Which viruses need their own replicases? (generally)
ALL RNA viruses are going to have to have their own replicase. ALL of them
41
(+) ssRNA virus
This might function as mRNA.
The cell can use this to make viral proteins.
The cell cannot make new genomes from it, so one of those viral proteins must be a replicase. So the replicase might not HAVE TO be packaged into the virions.
42
(-) ssRNA virus
The cell cannot use this.
| The virion must deliver a replicase enzyme into the cell to generate (+)RNA (mRNA)
43
dsRNA virus
The cell cannot use this.
The virion must deliver a replicase enzyme into the cell to generate (+)RNA (mRNA)
Cell pattern recognition receptors in your cells that are there to say ”is there double-stranded RNA in the cell and if there is let me die because there is a virus among us.” So, this will often trigger cell death so the virus often has to protect itself very well from triggering those responses
44
Where do DNA viruses replicate?
Most DNA viruses replicate in the nucleus where they can use the cell’s machinery for:
DNA replication (though most DNA viruses encode their own DNA polymerase)
DNA ➔ RNA transcription - regulated by transcription factors
RNA processing - a complex process only the cell can perform
Some DNA viruses induce cell proliferation and can cause cancer.
Herpes viruses encode some enzymes to allow them to replicate in neurons that are not proliferating - a drug target.
45
What DNA virus does NOT have to replicate in the nucleus?**
Pox Virus
46
Retrovirus Replication
Using reverse transcriptase, it converts (+) ssRNA into dsDNA, it integrates into the chromosomes, makes messenger RNA as if it were a cellular gene, and then you make new viruses.
47
Assembly, maturation and release
When a critical concentration of proteins accumulate, they self assemble into viral subunits or higher order structures.
Assembly of subunits or virions occurs in specific sites within the cell, the nucleus, the ER/Golgi, the cytoplasm, the plasma membrane.
Many viral proteins are generated first as a polyprotein which is then cleaved into mature proteins by either a viral or a cellular protease.
Assembly and maturation are attractive targets for antiviral drug development.
48
What do protease inhibitors do?
they prevent a cell that is infected from making new viruses that are infectious.
49
Naked Virus Release
all of the little viral particles continued to accumulate within the cell. So, most naked viruses crack open the cell. Some leave without killing the cell, but most of them kill the cell.
50
Patterns of viral infection and disease
Acute Infection
Latent Infection
Chronic Infection
51
Routes of entry into the body
```
Inhalation
Gastrointestinal Tract
Contact with mucosa (Nose
Mouth Urogenital tract)
Breaks in skin
Eyes
Before, during or after childbirth
```
52
Examples of Enteric Viruses
Picornaviruses (Polio, Enteroviruses, Coxsackievirus) Enteric Adenoviruses
Reoviruses - rotaviruses
Enteric Coronaviruses
HAV - Hepatitis A Virus - (causes acute disease)
53
Enteric Viruses
Area of infection: GI
Transmission:
- Eating and drinking
- Fecal-oral route: bad sanitation, unwashed hand to mouth contact
- High surface area of Small Intestines
Type of Viruses: Naked mainly - although coronaviruses are enveloped
54
Urogenital Tract - Sexually Transmitted Viruses
Vagina protected by mucous, low pH
Small abrasions (such as from sex), or lesions from other infections, allow viruses to enter past the mucosal layer.
55
Examples of Sexually Transmitted Viruses
```
Herpes Simplex Virus Type 2 (HSV-2) (HSV-1 through oral-genital contact)
HPV - Human Papillomaviruses
HIV - also via blood
HBV - also via blood
HCV - also via blood
```
56
Skin Viruses
Dead layer of epidermis is physical barrier, cannot be infected
Infection must occur through abrasions, cuts, bites, needle punctures Infection of epidermis leads to localized infection - no blood or
lymphatics to carry virus to rest of body
Dermis and sub-dermal tissues are highly vascularized
57
Examples of Skin Viruses
Papillomaviruses that cause skin warts - localized to basal cells
Rabies virus - bites through skin - virus replicates in neurons Vector borne (mosquitos):
Yellow fever virus
Dengue virus
Zika
58
Eye Viruses
Sclera and conjunctiva routes of entry Blinking washes conjunctiva
Injury, abrasions allow viruses to enter Conjunctivitis: localized eye infection
HSV-1 can infect cornea, resulting in blindness, spread to sensory ganglia - ocular herpes
Examples include HSV, Adenoviruses, CMV
59
Neurotropic viruses
Herpesviruses replicate in neurons and other cells as well.
Poliovirus enters and replicates mainly in the alimentary tract but can enter motor neurons and cause paralysis
Rabies spreads only via neurons.
Some viruses cross the blood brain barrier via infected macrophages They don’t infect neurons, but can cause neurologic problems
HIV
CMV - Cytomegalovirus
can enter the brain in immunocompromised people These are not strictly “neurotropic”
60
Examples of Neurotropic Viruses
Herpes Simplex Viruses (HSV-1, HSV-2)
aricella zoster virus (VZV)
(a.k.a. herpes zoster virus, chickenpox virus)
Poliovirus - it’s primarily a GI infection but can reach the CNS in ~1% of cases
Rabies virus
61
Perinatal Infections
Transplacental
CMV (cytomegalovirus)
Rubella virus - can cause congenital rubella syndrome - deafness, heart, eye problems
Zika
```
At time of birth
HBV
HCV
Herpes Simplex Virus Type 2 (HSV-2) HIV
Papillomavirus
```
So give the mother antivirals prior to birth for HBV, HCV, HSV-2, HIV
Breast Feeding
HIV
CMV
62
Blood for transfusions is tested for which viruses?
HIV-1, HIV-2
HBV HCV
HTLV-1, HTLV-2
West Nile Virus
63
TORCH Syndrome
Vertically transmitted agents, transplacental or perinatal:
T – Toxoplasmosis / Toxoplasma gondii
O – Other infections
R – Rubella
C – Cytomegalovirus
H – Herpes simplex virus 2 / neonatal herpes simplex
64
Typical Progression of Viral Replication and Disease
Barriers to infection
Entry into body
Initial replication at or near site of infection
if virus spreads, this causes primary viremia
Innate immune response
Replication in target tissue, inducing signs of disease and secondary viremia
Spread to other tissues and production of virus that can escape the host
Adaptive immune response
Resolution, or establishment of persistent infection/chronic disease
65
Incubation period
from initial infection to overt disease or the ability to detect the virus
66
Virulence
The relative degree to which an organism causes disease
Basically the two components of virulence:
1. How much can it spread
2. How much can it cause disease
67
what are the components of a virus that cause virulence?
- Virus replication efficiency: how fast, how many new virions are generated
- Virus effects on cells: death or interference in normal functions
immune responses
- Viral spread: how efficiently does the virus infect cells and new hosts
68
Viruses cause disease by
Cytopathic effects on infected tissues
Inducing Immune responses that cause symptoms.
Indirect effects that may be less understood. e.g. HIV causes generalized immune activation via poorly understood mechanisms and this results in long term damage to the immune system.
69
Pathogenesis influenced by the infected individual
Age
Nutrition
Immune health
Prior immunity
Other underlying pathologies
Genetics - e.g. MHC alleles
70
Mechanisms of how the virus kills the cell
Toxic viral components - adenovirus fibers, some HIV proteins. Production of large amounts of viral proteins can disrupt functions of organelles even if the proteins are not “intentionally” toxic.
Inhibition of cellular macromolecular synthesis - many viruses do this.
Herpes simplex viruses inhibit cellular DNA and mRNA synthesis, degrade cell RNA. Poliovirus inhibits cellular protein synthesis.
Syncytia - Herpes simplex, varicella zoster virus. HIV?
This is the fusion of cells caused by the virus spikes being expressed on the surface of infected cells coming into contact with the virus receptors on uninfected cells and causing fusion between the cells (instead of fusion between virus and cell).
Bystander killing: HIV envelope glycoprotein binds to CD4 on uninfected cells and induces them to undergo apoptosis.
Triggering cell suicide - cell’s have sensors to detect invading nucleic acid of viral genomes - dsRNA, cytoplasmic DNA, and then kill themselves via apoptosis or other programmed cell death mechanism.
