1
Q
definition of virus
A
- Are smallest infectious particles
- Range from 18 - 300 nm in size
- Consist of either DNA or RNA (but not both) and proteins with or without a lipid membrane coat
- Lack an independent metabolic system
- Require host cells for replication: true parasites
- Consist of an intracellular reproductive cycle, and an extracellular transmissive cycle
2
Q
viruses vs unicellular organisms
A
Unicellular organisms:
* Protozoa, fungi, bacteria, riskettsiae, mycoplasmas, chlamydiae
* Unicellular, both DNA and RNA, binary fission
Viruses:
* Obligate intracellular, either DNA or RNA (not both)
* Two life cycles: extracellular (transmissive, inert), intracellular (reproductive)
3
Q
unconventional viruses (subviral particles)
A
Extremely simple, replicating agents, either nucleic acid or protein
ex: viroids, virusoids, prions
4
Q
viroids/virusoids
A
subviral particle
viroid: replicate in nucleus
virusoid: replicate in cytoplasm
mostly plant pathogens
5
Q
prions
A
- subviral particle
- Proteins only, a small proteinaceous infectious particle (no nucleic acid genome).
- High resistance to heat, UV, irradiation, chemicals
- ex Prion diseases–Spongiform encephalitides
Prion proteins:
* Present in normal cells (PrPc)
* Abnormal, conformational aberration: amyloid formation (PrPsc)
6
Q
virus vs prion
A
7
Q
international committee on taxonomy of viruses naming classifications
A
Nomenclature: Orders, Families (subfamilies), genera(subgenera), species
* Order -virales example: Nidiovirales
* Family -Viridae example: Arteriviridae
–Subfamily -Virinae
* Genera -Virus, example; Arterivirus
–Subgenera
* Species Strain, example: Equine arteritis virus
order, family, genera in italics
8
Q
how are viruses named?
A
- describe characteristics
- describing members of the family
- describe site where it was first isolated
- describe the disease it causes
- describe the place it was discovered
9
Q
non enveloped vs enveloped viruses building blocks
A
Non enveloped:
* Protein subunit
* Structure unit
* Capsomer
* Capsid (coat or shell)
* Nucleocapsid
enveloped:
* Building blocks of non-enveloped viruses plus Envelope: peplomer/spike, matrix proteins, lipids
10
Q
spike/peplomer (glycoprotein)
A
important for host specificity, tissue tropism, fusion with cell membrane, infection, damages
11
Q
enveloped viruses
epidemiology, pathogenesis, immunology
A
- Epidemiology: short survival in environment, labile, “easier” to inactivate, often associated with seasonal diseases
- Pathogenesis: budding through infected cells, chronic/persistent infections
- Immunology: Glycoprotein antigens: VN, CMI, vaccine immunity
12
Q
non enveloped virus
resistance, pathogenesis
A
- Only nucleocapsid protein (“naked”, no envelope)
- More resistant: longer survival in environment, not seasonal disease, difficult to inactivate
- Pathogenesis: lytic cell infection: often associated with acute disease, less chronic
13
Q
nuclecapsid symmetry/shape
A
Icosahedral (Cubical): efficient package: 12 vertices, 30 edges, 20 triangles
Helical: All animal helical viruses are enveloped
14
Q
nuclecapsid symmetry types
A
Icosahedral (Cubical): efficient package: 12 vertices, 30 edges, 20 triangles
Helical: All animal helical viruses are enveloped
15
Q
chemical composition of viruses
A
Less complex than unicelullar or multicellular organisms
- Nucleic acid
- Proteins
- Carbohydrates (Glycoproteins)
- Lipids
16
Q
can viruses have DNA and RNA?
A
NO DNA OR RNA
17
Q
Are viruses diploid or haploid?
A
all are haploid except retroviruses are diploid
18
Q
which viruses are most likely to be enveloped?
A
helical
19
Q
which viruses have generally larger genomes?
A
helical
20
Q
structural proteins
A
part of virion
* Capsid/nucleocapsid: protecting genome
* Envelope protein (spike, matrix, etc)
* Number: ranging from 1 to >200
* Ligands (VAPs—viral attachment protein) for cellular receptors
21
Q
nonstructural proteins
A
enzymes, replication regulatory proteins, not part of virion
* Polymerases (transcriptases): dsDNA/dsRNA to mRNA
* Reverse transcriptase: retroviruses (from RNA to DNA)
* Integrase: integrates proviral DNA of retroviruses into host genome
22
Q
glycoproteins
A
- Oligosaccharides added to proteins in ER, move to Golgi complex, cell membrane, viral membrane through budding
- Ligands, enzymes, antigens
23
Q
viral carbohydrates
A
- In glycoproteins, glycolipids, muco-polysaccharides
- Most in viral membranes
- mostly in enveloped viruses
24
Q
endemic (enzootic)
A
Multiple, continuous transmissions, disease presence in a defined population/region/time
25
epidemic (epizootic)
Peaks in incidence **exceeding the endemic baseline**. Nature and degree of expected damage defines whether it is called epidemic (high damage) or not (low damage)
26
pandemic (panzootic)
worldwide epidemic
27
rate of disease
number of cases/population
Different diseases, different rates
28
incidence or attack rate
Number of cases over number of subjects over period of time (case:population ratio).
Acute, short duration diseases.
Denominator: population in a time frame: thus person-years or subject-weeks
29
prevalence
Insidious onset with unknown initial date.
Chronic, long duration diseases.
No time parameters, only number of cases in defined number of subject
30
parameters defining incidence in acute disease
* The proportion of the population which is susceptible (S/P)
* The proportion of the infected susceptible individuals (I/S)
* The proportion of the diseased infected individuals (C/I)
31
case/infection ratio
proportion of infections resulting in clinical disease
32
case/fatality ratio
proportion of infections resulting in lethal disease. Varied, characteristic
33
new biotypes
number of new changed characteristics of a virus
34
serological studies
detect Antibodies
clinical disease-silent, subclinical infections.
Not informative on current infections
prospective and retrospective
35
prospective serological study
* tracking events that are **supposed to happen in the future**
* placebo and treatment groups
* number of subjects depending on incidence
* very expensive
36
retrospective serological study
Cost-effective
only needing limited numbers of subjects
test how prevalent a disease is
37
incubation period
Moment of infection to onset of clinical signs
Short? long? variable?
38
generation time
* From moment of infection to first day virus shedding
* Mostly shorter than incubation period
* Influence in spreading disease
39
period of infectivity
* From first day to last day of virus shedding
* May or may not be longer than clinical signs
* Great influence in spreading disease
40
chronic viral disease
* Distinction between these time periods is difficult
* Little correlation among disease, generation time, infectivity
41
horizontal transmission
with or without vector, between the same or different host species
can be:
* direct contact: licking, rubbing, sexual contact (enveloped viruses)
* indirect contact: eating, bedding, needles (non enveloped viruses)
* common vehicle: water, feed
* airborne
42
route of transmission for enveloped vs non enveloped viruses
enveloped: direct contact (dont survive as well in environment)
non enveloped: indirect contact
43
vertical transmission
movement of virus from parents to their offspring during gestation via placenta, perinatally, colostrum, milk
ex: germline transmission: Virus integrated into genome of ovum, transcription and replication in offspring
Pass from generation to generation
44
germline transmission
Virus integrated into genome of ovum, transcription and replication in offspring
Pass from generation to generation
45
arthropod vector-borne transmission
can be:
* Biological vector: virus replicate, magnify in vectors, efficient transmission
* Mechanical vector: no virus replication in vectors, not efficient for transmission
46
biologica vector
virus replicate, magnify in vectors,
efficient transmission
47
mechanical vector
no virus replication in vectors,
not efficient for transmission
48
zoonotic disease
Viral diseases transmissible under natural conditions from vertebrate animals to humans
ex: rabies
49
what percent of human diseases are zoonotic?
60%
50
iatrogenic transmission
Patient to patient transmission under veterinary care during the interactions between the vets and the animals
preventable
51
nosocomial
transmission occurs while the animals are in hospital or clinic under the care of veterinarians
preventable
52
acute infection
* Rapid production of infectious viruses
* Rapid resolution and elimination of the infection (virus clearance) by the host
* Acute infections do not always produce disease
53
persistant infection
Infection not cleared efficiently
Virus particles are produced for a long period of time either continuously or intermittently for months or years
can be:
* Chronic infection: persistent infections that are eventually cleared
* Latent infection: persistent infections that last the life of the host
54
chronic infection
persistent infections that are eventually cleared
55
latent infection (latency)
* persistent infections that last the life of the host
* viral genomes integrated into cellular genomes, not expressed
* no infectious progeny
56
Recrudescence
* activation of latency (latent infection) due to various reasons (immunosuppression, stress, etc),
* new infectious virus progeny causing disease flair-up
* and new immune response
57
productive infection
resulting in infectious progeny
58
abortive infection
replication initiated, but not completed, limited gene expression: no infectious progeny
59
restrictive infection
permissivity is transient (individual cells) or proportional (cell population): few virions released
60
transforming infections
* DNA virus or retrovirus
* Infected cells display altered growth properties and proliferate faster
* Integration of virus genome into host cells in some infection
* Causing cancer in animals
61
patterns of shedding
* last phase of viral pathogenesis, mandatory for virus to survive in the host
* shedding through body openings/surfaces
* local infections = local shedding
* systemic infections = various shedding routes
* amount and timing of shedding defines outcome of infection
62
routes of virus shedding
* **Skin:** Not a major route, Contact, abrasions, wounds
* **Respiratory Secretions**: Very important, Numerous diseases, local, systemic, Shedding occur before, during, after clinical signs
* **Saliva:** Salivary gland, oral cavity (Rabies, FIV)
* **Feces**: GI tract viruses, Many also without intestinal signs: polio
* **Genital secretions:** Sexual activity, semen, mucus
* **Urine:** Rinderpest, FMD, canine hepatitis in kidneys, Hantaviruses: mice to humans
* **Milk:** Not an important route, Mammary gland replication, caprine arthritis-encephalitis
* **No shedding:** Not all virus replications ends with shedding, Encephalitis (CNS), retroviruses (germ line)
63
routes of virus shedding
* **Skin:** Not a major route, Contact, abrasions, wounds
* **Respiratory Secretions**: Very important, Numerous diseases, local, systemic, Shedding occur before, during, after clinical signs
* **Saliva:** Salivary gland, oral cavity (Rabies, FIV)
* **Feces**: GI tract viruses, Many also without intestinal signs: polio
* **Genital secretions:** Sexual activity, semen, mucus
* **Urine:** Rinderpest, FMD, canine hepatitis in kidneys, Hantaviruses: mice to humans
* **Milk:** Not an important route, Mammary gland replication, caprine arthritis-encephalitis
* **No shedding:** Not all virus replications ends with shedding, Encephalitis (CNS), retroviruses (germ line)
64
host range
receptors on animal tissues/cells
susceptible for wide range of infections or restricted infections
65
susceptibility
ability to become infected
66
permissivity
ability to replicate and produce progeny viruses
67
attachment
binding of virus attachment proteins (VAPs) on the surface of virion to the receptors on the target cell
68
virus attachment proteins (VAPs) non enveloped vs enveloped
Non-enveloped: part of the capsid or a protein extending from the capsid
Enveloped virus: spike/peplomer glycoproteins on the envelope
69
virus attachment proteins (VAPs) non enveloped vs enveloped
Non-enveloped: part of the capsid or a protein extending from the capsid
Enveloped virus: spike/peplomer glycoproteins on the envelope
70
receptors
proteins, carbohydrates on glycoproteins or glycolipids on the cell surface
Receptors on host cells determine host range, tissue tropism
71
penetration methods
Energy dependent, rapid
can be by:
* Translocation: non-enveloped virions
* Endocytosis: enveloped
* Fusion: some enveloped
72
uncoating
* Nucleocapsid is disintegrated
* Genome freed in cytoplasm
* Proteins disintegrate in cytoplasm
* Following uncoating, synthesis of viral proteins by cellular metabolism
73
steps of viral infection
1. attachment
2. penetration
3. uncoating
4. translation
5. macromolecular synthesis
6. assembly
7. maturation
8. release
74
translation
Viral mRNA translation to viral protein is essentially the same as cellular mRNA
Posttranslational modifications to become mature protein:
* Phosphorylation (nucleic acid binding)
* Fatty acid acylation (membrane insertion)
* Glycosylation
* Proteolytic cleavage, etc
75
macromolecular synthesis
DNA vs RNA viruses
transcription, translation, posttranslational modification, and viral genome replication
DNA viruses:
* Replicate in **nucleus** (except for poxvirus)
* Most use host cell’s **DNA-dependent RNA polymerase II** and other enzymes to **transcribe viral mRNA**
* Exception: poxviruses encode all enzymes in its genome
RNA viruses:
* Replicate in **cytoplasm**: must encode (or carry) necessary **enzymes for transcription and replication in their genomes**
* Exception: orthomyxoviruses, coronaviruses and retroviruses
76
assembly
viral proteins and glycoproteins start to replace cell membrane
77
maturation
very little/no original cell membrane left, only viral protein
budding starts
78
release
free infections virion released
79
cytopathic effect (CPE)
**morphological changes of infected cells** such as rounding, lysis, detachment, syncytia, inclusion bodies
cause:
* **Direct pathological injury** of the infected cells
* **Side effect** (altered metabolism due to virus replication)
80
effect of viruses on cell metabolism
* **Inhibition of Cellular Transcription Mechanisms:** Inhibition of transcription of cellular mRNA by cellular polymerase II enzyme
* **Inhibition of RNA Processing Pathways**: virus inhibits maturation of cellular mRNA, and converts cellular pathway for virus’s own use (capping, splicing, polyadenylation, etc)
* **Inhibition of Cellular Translation**: inhibit cellular mRNA translation as viral mRNAs are translated essentially the same as cellular mRNAs
* **Inhibition of Host Cell DNA Synthesis**: Viruses inhibit host-cell DNA synthesis to:
--- provide nucleic acid precursors for viral genome syntheses
--- re-direct host-cell enzymes for viral DNA synthesis
81
effect of viruses on cell metabolism
* **Inhibition of Cellular Transcription Mechanisms:** Inhibition of transcription of cellular mRNA by cellular polymerase II enzyme
* **Inhibition of RNA Processing Pathways**: virus inhibits maturation of cellular mRNA, and converts cellular pathway for virus’s own use (capping, splicing, polyadenylation, etc)
* **Inhibition of Cellular Translation**: inhibit cellular mRNA translation as viral mRNAs are translated essentially the same as cellular mRNAs
* **Inhibition of Host Cell DNA Synthesis**: Viruses inhibit host-cell DNA synthesis to:
--- provide nucleic acid precursors for viral genome syntheses
--- re-direct host-cell enzymes for viral DNA synthesis
82
effect of viruses on cell structure
* **Membrane fusion of neighboring cells**: leading to the formation of syncytia, a characteristic CPE for several enveloped viruses
* **Changing the permeability of the cell plasma membrane**: leading to increased influx of various ions, toxins causing **cell lysis**
* **Disruption of cytoskeletal fiber systems, microfilaments and microtubules:** causing rounding of cells, a frequent type of CPE
* **Cytoskeletal components incorporated into infected cell structures** either in cytoplasm (vaccinia or rabies virus Negri body) or in the cytoplasm and nucleus as inclusion bodies
83
skin entry into host
Natural barrier: epidermis (outer layer contains keratinized dead cells of stratum corneum)
Penetration/loss of barrier: cut, insect bites, abrasions, etc
Local infection, or systemic spread
Examples:
* HERPESVIRUS
* PAPILLOMAVIRUS
* POXVIRUS
84
ways a virus can enter host
* Respiratory tract
* GI tract
* Conjunctiva
* Genitourinary tract
* Skin (epidermis)
85
respiratory tract entry into host
Barriers:
* Mucus, mucociliary movement, neutrophils, macrophages
* IgA, CMI
* Droplet size, air currents, humidity, temperature (cold)
Many viruses (local or systemic infections), examples:
* ADENOVIRUSES
* CORONAVIRUSES
* HERPESVIRUSES
* CALICIVIRUSES
* ORTHOMYXOVIRUSES
* PARAMYXOVIRUSES
* PICORNAVIRUSES
86
respiratory tract entry into host
Barriers:
* Mucus, mucociliary movement, neutrophils, macrophages
* IgA, CMI
* Droplet size, air currents, humidity, temperature (cold)
Many viruses (local or systemic infections), examples:
* ADENOVIRUSES
* CORONAVIRUSES
* HERPESVIRUSES
* CALICIVIRUSES
* ORTHOMYXOVIRUSES
* PARAMYXOVIRUSES
* PICORNAVIRUSES
87
GI tract entry into host
Barriers:
* Low pH, proteases, bile salts, mucus, IgA, CMI
* Enzymatic enhancement
Many viruses, local or systemic infections, examples:
* ADENOVIRIDAE
* CALICIVIRIDAE
* **CORONAVIRIDAE**
* PICORNAVIRIDAE
* REOVIRIDAE
* TOROVIRIAE
* **NON ENVELOPED (survive harsh environment)**
88
GI tract entry into host
Barriers:
* Low pH, proteases, bile salts, mucus, IgA, CMI
* Enzymatic enhancement
Many viruses, local or systemic infections, examples:
* ADENOVIRIDAE
* CALICIVIRIDAE
* **CORONAVIRIDAE**
* PICORNAVIRIDAE
* REOVIRIDAE
* TOROVIRIAE
* **NON ENVELOPED (survive harsh environment)**
89
genitourinary tract entry into host
Barriers: mucus, IgA, CMI
Examples:
* Papillomaviruses
* Herpesvoruses
* Togaviruses
90
conjunctiva entry into host
Barriers: tear, IgA, IgG
Not a major route of transmission
Examples:
* Herpesviridae
* Adenoviridae
91
viremia (hematogenous spread)
* Vascular system: major pathway, systemic spread
* Entry site: limited replication
* Primary viremia: spread to distant organs (major replication sites)
* Secondary viremia: major clinical signs
* high viremia = virulence
**most efficient way to spread a virus systemically**
92
lymphatic spread
* less important than viremia, less effective
* Primary replication: epithelial cells, vascular system
* Spread: lymphatic vessels to other tissues
93
neural spread
Factors influencing the spread via CNS:
* primary replication site
* viremia (titer and length)
* duration of nerve tissue exposure, etc
Transport speed: 2 - 16 mm/day along the nerve axons (slow)
Ex: Rabies, polioviruses, herpesviruses, arboviruses
Different pathways may spread same virus to the same target organ
DWT exam 1
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