Exam 1 Flashcards
1
Q
List 6 ways that viruses impact domestic animals, humans, and science
A
- Common agents of Dz that you may encounter with some frequency
- High economic impact diseases
- Zoonotic diseases
- Viruses induce cancer in animals
- Newly emerging disease
- Tools for cell biology, gene therapy, vaccines
2
Q
What is a virus
A
an infectious agent comprised of one or more molecules of DNA or RNA surrounded by a protein coat, and sometimes a lipid envelope
3
Q
Replication
Bacteria vs Viruses
A
Bacteria: binary fission
Viruses: assembly line
4
Q
Genetic Material
Bacteria vs Viruses
A
Bacteria: Both RNA and DNA
Viruses DNA or RNA
5
Q
Protein production?
Bacteria vs Viruses
A
Bacteria: Yes
Viruses: No
6
Q
Energy production?
Bacteria vs Viruses
A
Bacteria: Yes
Viruses: No
7
Q
Requirement for Repro?
Bacteria vs Viruses
A
Bacteria: can replicate/divide on their own
Viruses: requires a cell
8
Q
Susceptible to abx?
Bacteria vs Viruses
A
Bacteria: Yes
Viruses: No
9
Q
List the 5 major primary sources of virus that affect animals
A
- Transiently infected animals
- wildlife
- environment
- persistently infected animals
- arthropods
10
Q
Ways to mitigate transmission of a virus
A
sanitation
vaccination
flea/tick prevention
quarantining
11
Q
define Virion
A
the intact, complete, physical infectious virus particle
12
Q
virus genome structure
A
linear or circular
single stranded or double stranded
13
Q
define capsid
A
protein that surrounds the viral genome
14
Q
capsid proteins are encoded by the ?
A
viral genome
15
Q
2 fundamental patterns of capsid proteins
A
icosahedral and helical
16
Q
which capsid pattern is common in spherical viruses
A
icosahedral
17
Q
which pattern is the most efficient way of forming a capsid shell?
A
icosahedral
18
Q
the more icosahedral capsule produced, the (smaller/larger) the virus
A
larger
19
Q
which capsid pattern is seen in all rod-shaped animal viruses?
A
helical
20
Q
viral genome forms a spiral in the capsid (icosahedral or helical)
A
helical
21
Q
describe an evelope
A
lipid and proteins that surround the capsid
(lipid bilayer and glycoproteins)
22
Q
all animal viruses that are helical are (naked/enveloped)
A
enveloped
23
Q
the lipid bilayer portion of an envelope is acquired by ?
A
budding through a host cell membrane (usually the plasma membrane)
24
Q
another name for glycoproteins within an envelope
A
spikes or peplomers
25
matrix
inner layer of envelope used to protect rigidity
26
nucleocapsid
additional layer surrounding the genome
27
tegument
"packing" between the capsid and envelope of herpesviruses
28
(enveloped/non-enveloped) viruses are more fragile
enveloped
29
5 ways that inactivate an enveloped virus
1. more heat labile
2. more vulnerable to oxidation
3. more susceptible to freezing and thawing
4. more susceptible to dessication
5. inactivated at low pH
30
capsid proteins (are/are not) highly conserved
are
31
Function of the capsid
1. mediated binding to cell membrane for entry
2. promotes uncoating after entry
3. packages genome during assembly
4. facilitates exit from the cell
5. + mRNA is translated by capsid proteins
32
Functions of the envelope
1. carry glycoproteins that are important for interaction with the host cell
2. binding to host cell receptors
3. fusion with cell membrane for entry
4. important in uncoating for some viruses
5. facilitate exit from host cells
6. viral GPs are often protective or neutralizing agents
33
define serotype
why is it important?
a set of viruses that can be distinguished from other viruses in the same species on the basis of antigenic properties.
important for understanding neutralizing properties
34
3 major viral characteristics/critera for classification of viruses
1. type of viral genome (RNA, DNA, +, -)
2. virion structure (enveloped or not, capsid symmetry)
3. strategy of replication
35
describe virus attachment
binding and attachment of the virion to the host cell
36
the viral attachment protein is on the (host cell/virion)
virion
37
the virus receptor is on the (host cell/virion)
host cell
38
describe penetration
normal cellular process for uptake of macromolecules via a specific receptor
39
penetration is used by (enveloped/naked/both)
both enveloped and naked viruses
40
can a naked virus undergo fusion?
no, requires an envelope
41
cells without appropriate receptors (are/are not) susceptible to infection by the virus
are not
42
what does penetration provide/facilitate
provides an environment that promotes fusion or uncoating
facilitates intracellular trafficking
43
how do naked viruses penetrate a cell membrane
membrane puncture
direct penetration (perforation or lysis)
44
how to enveloped viruses penetrate cell membranes?
membrane fusion using fusion proteins in the virus envelope
45
how do fusion proteins work?
they contain hydrophobic domains (fusion peptides) that are inserted into the cell membrane. the inactive fusion peptide needs to be activated by a conformational change
46
how is a fusion protein activated? what follows activation?
it is cleaved by a host protease at the cleavage site -> activation and membrane fusion
47
describe uncoating
removal of capsid, release of the viral genome (DNA or RNA)
48
is uncoating independent of penetration?
can occur simultaneosly or independent of penetration
49
describle biosynthesis
synthesis of mRNAs recognized nby the cell translation machinery - makes proteins for replication
50
goal of biosynthesis
replicate the viral genome! new genomes for packing into virions
51
describe assembly
virus proteins and genomic nucleic acid must co-localize and assemble into a functional virus particle
52
how are non-enveloped viruses released?
generally requires cell lysis
53
how are enceloped viruses released
may or may not require cell lysis.
can undergo budding which is not lethal to the cell
54
Viral Growth curve: What is A?
What steps of viral replication does this step match with?
Virus Absorption
Attachment and Penetration
55
Viral Growth curve: What is B/D?
What steps of viral replication does this step match with?
Eclipse Period
Virus uncoating and sythesis of genome and proteins
Uncoating and biosynthesis
56
Viral Growth curve: What is C?
What steps of viral replication does this step match with?
Virus assembly, maturation and virion release
Assembly and Release
57
Viral Growth curve: What is happening at E?
virus accumulating intracellularly
58
Viral Growth curve: What is happening at F?
virion begins to accumulate extracellularly
59
Viral Growth curve: What is happening at G?
large increase in extracellular virus - a lytic virus will burst
60
describe the eclipse period
there are no full virus particles. The virus has opened its capsid or envelope so the parts are disassembled. No detectable virions at this stage
61
What does the viral growth curve tell us about a virus?
1. virus production is step wise (not linear or exponential)
2. the replicating entity is actually a virus (only viruses have an eclpise phase)
3. how fast the virus replicates
4. how many progeny particles are pruduced per cell (burst-size or yield)
62
what is the *primary* determinant of host cell specificity?
the appropriate receptor
63
What steps of virus replication can Ab interfere in?
Attachment and penetration (neutralizing Abs)
64
Change in a receptor can result in?
expansion of tissue tropism, host range, and emerging disease
65
How can Protease cleavege site and distribution of cellular proteases affect a virus
they can affect tissue distribution and pathogenicity (Ex: low pathogenic vs high pathogenic avian influenza)
66
What is involved in viral biosynthesis for DNA viruses?
DNA viruses usually use **host cell** proteins and enzymes to make additional DNA that is transcribed to messenger RNA (mRNA) by **DNA-dependeent RNA-polymerase** , which is then used to direct protein synthesis.
67
What is involved in viral biosyntheses for RNA viruses?
RNA viruses use their own polymerase (**RNA-dependent RNA-polymerase**) to transcribe their genome into mRNA
68
both RNA and DNA viruses must be transcribed into (?), then to viral proteins
(+) mRNA
69
why must replication of **all** viruses result in production of positive sense mRNA?
all viruses must make mRNA that can be recognized by the host translational machinery
70
two strategies that RNA viruses employ to produce positive sense mRNA
use virus encoded enzymes (polymerases) for replcation
**(-) RNA --*RdRp*--> (+) RNA --> protein**
or use a reverse transcriptase
**RNA --*RT*--> DNA --> (+) RNA --> protein** only retroviruses can do this
71
(DNA/RNA) viruses are more prone to developing genomic mutations
RNA
72
Why are RNA viruses more prone to developing genomic mutations?
lack of proofreadinf functions leads to a higher rate of error during RNA virus genome replication
73
why are viral encoded polyproteins and polymerases excellemt targets for developing antiviral therapeutics?
the pathways are not normally found in mammalian cells and are necessary for viral reproduction
74
Where does cell assembly occur for RNA viruses?
in the cytoplasm of the cell (they bring their own enzymes! don't need access to the nucleus)
75
Where does cell assembly occur for DNA viruses?
in the nucleus of the cell
76
How is location of viral cell assembly useful in indentifying viral infection in cells?
the site of assembly is often where diagnostic inclusion bodies are seen by light microscopy
77
what is a susceptible cell
the cell is sensitive to infection by a particular virus. largely a function of presence or absence of receptors
78
what is a permissive cell
the cell is able to support complete replication of a particular virus. this is a function of the interal biochemistry of the cell.
79
for an infection to be successful, the cell has to be (permissive/submissable)
both!
80
Cytolitic infections: CPE?
Yes
81
productive persistent infections: CPE?
little to none
82
latent persistent infections: CPE?
usually no effects on cell
83
Cytolytic infections: continued cell division?
cell death
84
productive persistent infections: metabolic change?
little metabolic change
85
latent persistent infections: metabolic change?
usually no effect on cells
86
cytolytic infections: alter cell specialized functions?
inhibition of protein, RNA and DNA synthesis
87
productive persistent infections: alter cell specialized functions?
loss of some specialized functions
88
productive persistent infections: continued cell division?
cells continue to divide
89
cytolytic infections: viral productivity?
produces virus
90
productive persistent infections: viral productivity?
virus produced
91
latene persistent infections: viral productivity?
no virus produced, but can be induced
92
define cytopathic effects (CPE)
morphologic changes observed in cell culture due to virus infection
93
What does CPE tell you about a sample submitted to a diagnostic lab?
often, CPE is a characteristic of a particular virus and can be useful in prelimiary diagnostics
94
Types of Cytolytic CPE
1. cell shape changes
2. cell lysis
3. formation of Syncytial or "giant" cells
4. viral inclusion bodies
95
define viral latency
virus infection where the viral genome is maintained but new viral gene products are not made and no virus is produced
96
it there a dianostic test for a latent virus?
No, but PCR can tell you if infection is present (just cant tell you if its latent or productive)
97
What diagnotic test can you use to confirm a productive virus?
ELISA for Ag on whole blood, or PCR for viral genome on whole blood (v-RNA)
98
define proto-oncogene
Normal cellular gene whose product promotes cell growth (growth factors, growth factor receptors, proteins for signal transduction, transcription activators, cell cycle regulators)
99
define oncogene
cellular gene that produces autonomous cell growth in cancer cells (due to mutation or overexpression)
100
define viral oncogene
mutant of overexpressed version of a proto-oncogene carred by a virus
101
What kind of virus typically carries viral oncogenes?
retroviruses
102
define viral transforming gene
viral gene that mimics a cellular oncogene but evolved independently and is genetically distinct
103
define oncoprotein
protein that is constitutively active to promote autonomous cell growth
104
What produces oncoproteins
transcription of oncogenes, viral oncogenes and viral transforming proteins produce oncoproteins
105
define transduction
transfer of genetic material from one cell to another cell by a virus (retroviruses)
106
3 ways that DNA viruses promote tumor development
1. inactivation of tumor suppressor genes
2. bind growth factor receptors and activate signaling pathways
3. produce oncoproteins that drive or limit transcription
107
how do retroviruses transform cells?
by making mistakes in replication and producing oncogenic products
108
describe insertional cis-activation of cellular proto-oncogenes
retrovirus genome integrates near a cellular proto-oncogene.
the expression of c-onc is under the control of the virus LTR
LTR contains the viral promoter - where transcription factors bind and promote transcription. this is why **all retroviruses** have the potential to become neoplastic
109
describe transactivation by virus encoded proteins
during replication, cellular proto-oncogene is mistakenly acquired by the retrovirus genome. Genes are no longer under control of the cell, but are under control of the virus LTR.
The oncogene can be transferred from one cell to another by the virus
110
define pathogenicity
ability of the virus to cause Dz (YES OR NO). contributed by both the host and the virus
111
define virulence
the relative measure of pathogenicity (the DEGREE of damage) a propety of the virus.
112
management strategies to keep majority of infections resulting in inapparent Dz
vaccinate, provide good nutrition, manage dose (environmental)
113
changes in virulence are responsible for....
emergence and re-emergence of viruses, host range expansion, and overcoming the host immune response
114
how can a highly virulent virus shift the "iceberg"?
highly virulent viruses often establish infection in a greater number of hosts than they cause disease
115
3 principle factors that determine the outcome of viral infection and severity of disease
1. genetic features of virus
2. route and dose of inoculum
3. host factors
116
What factors at the individual host level can influence disease outcome?
immunity (Vx or not), nutrition, age, sex, breed...
117
what is DEED and how does it influence the risk of viral transmission
Dose, Envelope or not, Environment, Distance
* Envelope matters when considering disinfection
* enviro: cold, wet and windy environments tend to increase the risk of transmission
* distance between infected individuals
118
transient infection duration
generally short
119
are transient infections cleared?
the virus is eventually eliminated from the host
120
(transient/persistent) infections may be self-limiting, and/or controlled by innate or adaptive immune responses
transient
121
are persistent infections cleared?
no
122
persistent infection Dz patterns
variable - from subclinical to progressive
123
5 mechanisms that viruses use for persistent infection in a host
1. immunological tolerance
2. latency
3. infection of immune cells
4. infection of tissues in immunologically privilaged sites
5. escape from competent adaptive immune response (antigenic variation)
124
3 major anatomic portals that diseases use to enter/exit a host
mucosal (GI, resp, urogenital, conjunctiva), skin, veritcal transmission
125
barriers at mucosal surfaces
1. mucociliary clearance
2. acid, bile, proteaes
3. rapid turnover
4. peristalsis
126
how do viruses enter skin
via abrasions or penetrations (injuries, mechanical insults, arthropod vectors)
127
what is vertical transmission
without passage through the environment - usually refers to transmission prior to birth (in germ line of fert. eggs, across the placenta, during passage through the birth canal)
128
consequences of vertical transmission
abortion, congenital Dz, persistent infection, neoplasia
129
portals of exit
may or may not be the same sites of entry. include resp droplets/aerosol, feces, saliva, skin, feather follicle, urine, semen and milk
130
portals of exit for localized infections
typically the same as site of entry
131
describle immunological tolerance and give an example
virus continually divides but the viral antigens are recognized as self. Ex: BVD
132
describe latency
allows the virus to persist in animal populations (silent carriers) for life without showing clinical signs
133
what are some immunologically privilaged sites?
gonads, brain, (protected)
GI tract, resp, skin (commonly present with antigens, have a high threshold for immune activation)
134
3 ways that viruses escape from a competent adaptive immune response
1. ineffective non-neutralizing Ab (animals make Ab but against the wrong Ag)
2. change neutralizing Ag (antigenic variation)
3. interfere with antigen presentation (blocks pathways of Ag presentation by MCH I and II)
135
how does restricted viral gene espression aid in viral persistence
evades the immune system through the "trojan horse" model
absence (or minimal) viral protein production allows virus to hide from immune effector molecules
136
localized viral infection: site of replication?
at or near th body surface through which they entered
137
localized viral infection: incubation period?
usually short
138
localized viral infection: where does lesion formation and shedding occur?
in the same organ as viral entry and replication
139
localized viral infection: spread
cell to cell
140
localized viral infection: viremia?
no
141
localized viral infection disease severity vs systemic disease severity
cannot compare. localized does not mean less severe
142
systemic viral infection: virus spread, shedding
viruses spread from the entry site through lymphatic and hematogenous dissemination to cause generalized infections in specific organs. sites of entry, the 'target' organ, and shedding site may or may not be the same.
143
systemic viral infection: incubation period
longer than localized
144
systemic viral infection: when is peak viremia?
second viremia
145
primary viremia
the first viremic period (transient and subclincal)
146
secondary viremia
large amounts of virus in bloodstream. Peak viremia, Very detectable
147
4 factors that govern whether a virus remains localized or spreads sytemically
1. directional release - how a virus enters/exits a cell
2. availability of susceptible and permissive cells in deeper tissues
3. macrophage/monocyte susceptibilty and permissivity
4. temperature range of the virus
148
release from apical surface of cell (Localized or Systemic)
localized
149
release from baslolateral surface of the cell (Localized or Systemic)
Systemic
150
virus-macrophage infection (Localized or Systemic)
Systemic
151
virus can't replicate at higher body temps - (Localized or Systemic)
Localized to cooler areas (resp/oral, mucosa, skin)
152
what type of immune cell is KEY in a lot of systmic infections?
macrophages
153
2 major factors that contribute to the termination of an active viral infection
1. depletion of susceptible cells
2. the immune response
154
depletion of susceptible cells in more important for (localized/systemic) infections
localized
155
the innate immune response is more important for (localized/systemic) infections
localized
156
the adaptive immune response is more important for (localized/systemic) infections
systemic
157
peak viral replication occurs prior to febrile response and other clinical signs in (localized/systemic) infections
both!
take samples early for both types of infection.
158
how does the innate immune system detect viral infections?
PRRs (TLRs and RLRs) recognize PAMPs on the virus
159
Type I IFNs are produced by
produced and secreted by virus infected cells
160
Type I IFN repsonse time to infection
rapid! within 3-4 hours
161
role of Type I IFNs
protects neighboring, uninfected cells - upgregultes IFN-stimulated genes which leads to enhanced defenses against viral invasion and replication
162
Type I IFNs (are/are not) specific to a particular virus
are not
163
What causes fever during viral infection and how does it benefit the host?
* pro-inflammatory cytokines!
* elevated temperature inhibits viral replication
* increased rate of chemical/enzymatic reactions
* increased blood flow to inflamed areas
* increased speed of inflammatory processes
164
Phagocytes and NK cells are actived by
pro-inflammatory cytokines
165
Phagocytes and NK cells (are/are not) anitgen specific
are not
166
Phagocytes and NK cells target what type of cell
mostly infected cells
167
Phagocytes and NK cells time to response
48-72 hours
168
role of NK cells in infection
kill infected cells
169
role of phagocytes in infection (macrophages, neutrophils)
* phagocytose and degrade virus infected cells or debris
* relase vasoactive substances that increase speed and intensity of immune response
* secrete cytokines important in induction of the adaptive immune response
170
role of APCs in infection
capture, process, and present Ag on their surface to T-cells
171
Humoral immunity: extracellular or intracellular viruses
extracellular
172
Cell-mediated immunity (CMI): extracellular or intracellular viruses
any viruses, but more effective against intracellular
173
3 types of Ab mediated host defense mechanisms
1. neutralization
2. opsonization
3. ADCC
174
describe Ab neutralization
Ab binds to virions and blocks infection by preventing attachment, penetration, uncoating or release
175
describe opsonization - what is a downfall to this?
Abs bind to virus and assist phagocytic cells with update and intracellular destruction of viruses
**some viruses take advantage of this to enhance entry into host cells (ADE - Ab dependent enhancement of infectivity) - can increase Dz severity
176
describe ADCC (Ab-dependent cell-mediated cytotoxicity)
Ab binds to virus infected cells expressing surface Ag and assists immune effector cells in recognizing and killing infected cells
177
describe Ab neutralization mechanisms
1. steric hinderance (physically interferes with virus ligant attachment to receptors)
2. interfering with fusion (enveloped) or stablizing the capsid (non-enveloped)
3. lysis of the virion before it can infect a cell
4. Ab-mediated aggregation
178
How to CTLs help clear infections. When are they most important?
* Activated CTLs release granzymes/perforin and kill virus-infected cells through apoptosis
* CTL does a better job controlling the spread of viruses *after* they gain entry. They are most important in recovery from established infection.
179
how can the immune response contribute to the pathogenesis of viral diseases like FIP?
excessive immune response can lead to depletion of things like T-cells, macrophages... etc
180
goal of vaccination
Prevent or reduce disease, not necessarily to prevent infection.
181
Viral Vx prevent or modify disease (with/without) preventing infection
without
182
most common form of live virus vx?
modified live
183
goal of modified live Vx?
The goal is to reduce virulence but maintain induction of protective immunity (And stimulation of natural immune pathways)
184
how to develop attenuated virus strains?
genetically enginerred, temperature sensitive, empirically derived
185
define DIVA
Differentiating Infected from Vaccinated Animals
186
define replication competent virus vectors
usually, large DNA viruses are used as the vector. Can undergo replication (cause an “infection”) within the vaccinated animal, but generally non-pathogenic
187
define replicaton defective virus vectors
can only undergo a single round of replication. Do not produce infectious virus, Less chance of virus transmission, but more Vx needed. (boosters)
188
types of replicating viruses
1. live
2. modified live
3. virus-vectored (replicating)
189
types of non-replicating viruses
1. inactivated
2. virus vectored (non-repliacting)
3. virus component (protein subunit Vx, virus-like particle Vx, Nucleotide Vx)
190
what is a protein subunit Vx
composed of individual protective protein subunit of the virus
191
What is VLP Vx
Virus-like partice. non-infectious. lack nucleic acids (empty capsid). Morphologically resemble the real virus
192
what is a nucleotide Vx
viral DNA or mRNA. Does not insert into the host genome, but stimulates an immune response
193
define adjuvant
chemicals or other compounds added to a Vx to heighten/enhance the immune response
194
adjuvant is especially important for what types of Vx?
inactivated/non-replicating Vx
195
Adjuvant mechanisms of action
* Induce cytokine/chemokine responses
* Enhance recruitment of innate immune cells -> adaptive immune cells
* Enhance Ag uptake and presentation
* Enhance Ag transport to LNs
* Alter quality and quantity of immune response
196
(replicating/non-replicating) Vx are more effective
replicating
197
(replicating/non-replicating) Vx are safer
non-replicating
198
(replicating/non-replicating) Vx are more stable (storage)
non-replicating
199
(replicating/non-replicating) Vx stimulate a longer lasting immune response
replicating
200
(replicating/non-replicating) Vx spreads across mucosal surfaces during replication better, thus timulating a greater mucosal immunity
replicating
201
(replicating/non-replicating) Vx yield greater anigenic mass because of the amplifyig effect
replicating
202
(replicating/non-replicating) Vx have concern for return to virulence
replicating
203
(replicating/non-replicating) Vx are more dangerous to pregnant animals
replicating
204
barriers to producing antiviral drugs in vet med
* Early detection is challenging as animals are often brought to the vet after the viral infection has progressed.
* clincial symptoms usually later in infection = missed opportunited for Tx
* antivrial drugs are specific - determining the specific virus responsible for the disease takes time
205
2 modes of action for antiviral drugs
prevent infection - prophylaxis/pre-exposure prophylaxis (PrEP)
stop/limit infection (Therapeutic)
206
Why is there a limited repertoire of antivirals?
1. saftey/efficacy issues
2. specificity of viral agent
3. insufficent knowledge base/challenges of in vitro replication
4. cost (low profits for pharmaceutical companies)
207
main 4 mechanisms of action of antiviral drugs
1. block uncoating
2. block genome synthesis
3. block protein synthesis
4. block release
