Mouse Pathology Review - DNA Viruses Flashcards
(144 cards)
1
Q
What kind of virus is Ectromelia virus
A
orthopoxvirus
2
Q
What does ECTV stand for?
A
Ectromelia virus
3
Q
Which mice are susceptible to ECTV?
What is a common presentation for these mice?
A
- C3H
- A
- SWR
- DBA
- CBA
BALB/c
They die acutely
4
Q
Which mice are moderately resistant to ECTV?
A
SJL and AKR
5
Q
Which mice are highly resistant to fatal infection of ECTV?
A
C57BL/6 mice
6
Q
What is ECTV resistance based on?
A
Many genes, particularly variations in immune cells and cytokines?
7
Q
Clinical signs of ECTV?
A
- vary from ruffled fur to prostration to death in a matter of hours
- Generalized rash that may last for weeks and leave scars
- subclinical in resistant strains
8
Q
Common gross lesions of Poxvirus
A
- Alopecia, cutaneous erythema, erosions (rash), conjunctivitis, swelling, and Dry gangrene of extremities leading to amputation (ectromelia)
- swollen, friable livers w/ pinpoint white/red foci
- “Tiger stripe spleen” - splenic fibrosis -
- intestinal hemorrhage of upper small intestine
9
Q
Histo lesions of ECTV
A
- *** Foci of coagulative necrosis in liver, spleen lymph nodes, Peyer’s patches, thymus
- ***erosive enteritis
- *** epidermal hyperplasia, hypertrophy and ballooning of epithelial cells
10
Q
Strains resistant to ECTV will show more ____, while more susceptible strains will show more ___ of lympoid tissue
A
- hyperplasia
- necrosis
11
Q
Types of Inclusion Bodies of ECTV
A
Type A: Eisinophilic, intracytoplasmic inclusion bodies in epithelial cells of the skin
— Marchal bodies
— epidermal skin cells, hepatocytes at periphery of necrosis
Type B: basophilic, intranuclear inclusion bodies potentially in any affected cell, but difficult to see
12
Q
DNA viruses tend to make intranuclear inclusion bodies. What sets ECTV apart?
A
can be intracytoplasmic and intranuclear
13
Q
Diagnosis of ECTV
A
- ELISA
- Histopathology
- PCR, immunofluorescence
- Hemagglutination assay (HAI)
14
Q
Pathogenesis of ECTV
A
Skin invasion via trauma to skin -> local invasion and multiplication -> replication in regional LN -> hematogenous spread to major organs (primary viremia) -> replication in spleen and liver -> secondary viremia -> targets sites like skin, kidney, lung, intestine, and other organs and causing focal infections
15
Q
Transmission of ECTV
A
- Direct contact and cutaneous trauma (NOT contaminated animal products)
- Not highly contagious
16
Q
Repro concerns for ECTV
A
- maternal antibodies protect against disease, but not infection
- ECTV infects placenta and fetuses, leading to fecal death
17
Q
Prevention and Control of ECTV
A
- Decontamination: viral particles stable in environment
- Quarantine and/or Depopulation
- Vaccination w/ vaccina virus (will not always prevent infection but will lower it)
18
Q
Research impacts of ECTV
A
Potential massive loss of life in susceptible strains
19
Q
Types of Mouse Adenoviruses
A
- Murine mastadenovirus-1 (MAdV-1)
- Murine Mastadenovirus-2 (MAdV-2)
20
Q
typical presentation in of MAdV-1 and MAdV-2 in immunocompetent mice
A
subclinical
21
Q
Which cells does MAdV-1 target?
A
- Monocyte-macrophage lineage
- Renal distal tubular cells, respiratory epithelium, adrenal cortical cells, microvascular endothelium
22
Q
Which cells are important for clearing MAdV-1 infection?
A
B-cells
23
Q
Which cells are important for fighting disease and what else can they do?
A
T-cells; can also contribute to pathology (T-cells killing the virus may determine severity of clinical disease)
24
Q
How is MAdV-1 shed?
A
- in the urine
- Direct contact and nasal secretions
25
Which strains develop hemorrhagic encephalitis with MAdV-1 infection?
- C57BL/6
- DBA/2
- SJL
- SWR
- CD-1
26
Which strains develop disseminated disease with hemorrhagic encephalomyelitis?
B6-Rag1
27
Which strains develop a fatal disseminated disease with focal hemorrhagic enteritis and microvascular fatty change (Reye's-like syndrome)?
BALB-scid and BALB-scid/beige
28
Which strains develop progressive wasting, disseminated infection, and duodenal hemorrhage?
Athymc C3HH3N-nude
29
Which type of brain matter is more affected by MAd-V1?
white matter -- "a lot of it is being 'unable to relax'"
30
Clinical signs of MAdV-1
- runting
- Dehydration
- CNS signs from white matter injury
--- rigid tails, hypermetria, paraphimosis, ataxia, urinary bladder distention
31
Gross lesions of MAdV-1
- thymic involution
- necrosis in liver, spleen, and other organs
32
Histo lesions of MAdV-1
- endothelial necrosis and hemorrhage
- Intranuclear inclusions in foci of necrosis and hemorrhage in vary types of organs
33
T/F Rats will seroconvert and are susceptible to MAdV-2
False; they will not seroconvert
34
How is MAd-V2 shed?
in the feces
35
Tissue tropism of MAdV-1
multiple: intestine, salivary glands, spleen, brain, myocardium, brown fat
36
Tissue tropism of MAdV-2
enterotropic
37
Prevalence of MAdV-1 in vivaria
historic only
38
Prevalence of MAd-V2 in vivaria
natural infection in modern vivaria, low
39
Clinical signs in natural infection of MAd-V1
none described
40
Clinical signs in natural infection of MAdV-2
runting of suckling mice
41
Clinical signs in experimental infection of MAdV-1
severe with pup infection: runting, lethargy, scruffy, death in 10 days, wasting disease in nude mice
42
Clinical signs of experimental infection of MAdV-2
Absent except for runting of suckling mice
43
Clinical signs of MAdV-2
Rare, aside from runting of suckling pups
44
Histopathological findings of MAdV-2
intranuclear inclusions in intestinal epithelium of infant mice > adult mice (apical location, rather than basal)
45
Transmission of MAdV-2
shed in feces
46
Diagnosis of MAdV
- Serology
- Intranuclear inclusions in intestine are pathognomonic for MAdV-2
47
Prevention and Control of murine adenoviruses
- Serologic monitoring
- Segregate infected colonies until infection is over (MAdV-2 only)
- Rederivation
"MAV1 - either suck it up and accept its presence or cull"
"MAV-2 - self-limiting, so can segregate colonies"
48
Research concerns of MAdV
primarily pathogenicity impact on immunodeficient mice
49
DDx for ECTV
causes of hepatitis, such as
- MHV vs Tyzzer's dz vs salmonellosis vs other
Skin lesions
- bite wounds vs. trichotillomania vs. hypersensitivity vs. other forms of dermatitis
gangrene or digit / tail amputation
- trauma vs. ringtail
50
Which subcategory of herpesvirus is the worst?
alpha-herpesviruses
51
What are the three subcategories of herpseviruses
- alpha-herpesviruses
- beta-herpesviruses
- gamma-herpesviruses
52
What is the other name for Murine herpesvirus 1?
Mouse Cytomegalovirus (MCMV)
53
Clinical signs of natural infection of MCMV?
subclinical in lab animals
54
Clinical signs of Experimental infection of MCMV?
multisystemic necrosis, inflammation, and death of neonatal mice
55
Histopath lesions of MCMV?
- enlarged cells with intranuclear and intrcytoplasmic inclusions (nucleus is easily 10x normal size), particularly in the **salivary glands, esp. the submandibular gl.**
- Lymphoplasmacytic infiltrates
56
Strains resistant to MCMV
- C57BL/6
- B10
- CBA
- C3H
Resistance is associated with the H-2k haplotype
57
Strains susceptible to MCMV
- BALB/c
- A
Will see worse necrosis and inflammation in organs of T-cell-deficient mice
58
Pathogenesis of MCMV
experimental inoculation -> viremia and multisystemic dissemination to lung, heart, liver, spleen, gonads, and salivary glands ->rapid clearance from every but PERSISTENT in salivary glands. Intranuclear inclusions can be seen in acinar epithelial cells
59
Diagnosis of MCMV
- Histopathology
---in situ hybridization to assist
Serology and PCR not reliable bc subclinical in most situations
60
what is the major target of MCMV
macrophages; blood monocytes are important for viremic phase of infection
61
Which cell type helps to clear MCMV
NK cells
62
T/F MCMV is a latent infection, which means that stress or immunosuppression can result in reactivation of the virus
true
63
T/F MCMV readily crosses the placenta
false
64
What can MCMV infection cause in pregnant mice?
Fetal death and resorption, delayed birth, experimentally infected mice.
65
Transmission of MCMV
- direct contact with infected mouse or bodily fluids (saliva, urine, tears)
- contaminated animal products
- sexual and in utero transmission due to infection of gonads
66
Prevention of MCMV
KEEP WILD RODENTS OUT
67
Research concerns of MCMV
- immune suppression by virus
- reactivation of latent persistent infection by either lymphoproliferative stimuli or immunosuppression
- potential for immune-complex glomerulonephritis in persistent infections
- synergistic effect with Pseudomonas aeruginosa
68
What is another name for murine herpesvirus 3?
Mouse Thymic Virus (MTV)
69
Prevalence of MTV
wild mice: common
Lab mice: rare
70
Tropism of MTV
lymphocytotrophic - selectively targetrs CD4+ cells
but some infection/replication in thymic epithelial cells and macrophages
71
Where is MTV virus shed
in saliva
72
Why are serology and PCR-based diagnosis not used for MCMV
they are not used because it is assumed that the virus has a very low prevalence
73
Clinical signs of MTV
it is subclincal, no CS
74
Gross findings of MTV
Acute thymic necrosis in neonatal mice (most susceptible in first 6 days of age)
- infection is persistent, but thymus will eventually return to normal size
75
Histopath lesions of MTV
- necrosis of thymic lymphocytes, and lesser necrosis of lymphocytes in LNs and spleen
- intranuclear inclusion bodies
- granuloma formation in recovery
76
Strains susceptible to MTV
- BALB/c and A strains can get gastritis if infected as neonates
- Autoimmune oophoritis and anti-thyroglobulin development in other mice strains
77
Research implication of MTV
immunosuppression
78
What effect will MTV have on athymic nude mice?
none really, since it has a destructive effect on T lymphocytes, which they lack
79
Tissue tropism of MCMV
multiple tissues, but histopath in salivary glands
80
Tissue tropism of MTV
infects salivary glands; lesion only in thymus, LN, spleen
81
MCMV Prevalence in vivaria/reservoir
rare / wild mice
82
MTV prevalence in vivaria / reservoir
rare / wild mice
83
Is latent infection of feature of MCMV
yes
84
is latent infection of feature of MTV
yes
85
Limitations to detection of MCMV
salivary gland lesions not always present; mice may not seroconvert
86
limitations to detection of MTV
mice infected as neonates may not seroconvert
87
Name two mouse parvoviruses
Minute Virus of Mice
Mouse Parvovirus
88
Which mouse parvovirus is more prevlant?
MPV > MVM (75% of parvoviral infections)
89
T/F immunity to one parvovirus confers immunity of the other
false; it does not
90
Which structural capsid protein contributes the most antigenic and biologic differences between MVM and MPV
VP2
91
Pathogenesis of MVM and MPV
- S-phase-dependent (so young animals are more affected (rapidly dividing cells present))
- oral inoculation -> replicate in intraepithelial lymphocytes, lamina propria, and endothelium of SI -> disseminate to multiple organs (kidney, intestines, lymphoid tissue, liver, lung (lesser extent)
92
T/F rodent parvoviruses cause intestinal disease
false; the intestinal crypts lack proteins for viral binding and infection
93
Site of initial replication of mouse parvoviruses
In lymphocytes
94
T/F clinical signs are seldom present in mouse parvovirus infections
technically true, as MVM and MPV do not carry clinical signs
95
transmission of murine parvoviruses
feces and urine via oronasal inoculation
96
What cells have the highest tropism for murine parvoviruses
- endothelial cells
- hematopoietic cells
- lymphoreticular cells
-- MVM also targets erythrocytes and can replicate in renal tubular epithelium
97
Clinical signs of MVM and MPV
none, infections are typically subclinical
Experimental infections can cause disease in neonates and some strains
98
Gros lesions of MVM and MPV
- MVM: possible cerebellar hypoplasia (targeting granular layers) in neonates
- MPV: usually none.
99
Histopath lesions for MPV and MVM
generally none, aside from inclusion bodies
100
What clinical signs can be seen with MVMi variant of MVM? what is the other name?
mortality in neonates due to hemorrhage, hematopoietic involution, and renal papillary infarction
immunosuppressive strain of MVM
101
Which strains are susceptible to infection with MVM/MVMi?
- DBA/2 neonates susceptible to severe disease
- SCID adults can die and/or develop severe leukemia
- C57BL/6 neonates are resistant
102
MVM has is more ______ in duration, which MPV causes _______ infections with ____ shedding and possible immunologic changes
- limited
- persistent
- prolonged
103
Diagnosis of MPV and MVM
- serology (primary method) - tests for VP2 (specific for each parovirus)
PCR, ISH, IHC also possible but more reliable during active infections
104
Which tissue is the most reliable source for PCR detection of MVM and MPV
mesenteric lymph nodes
105
Transmission of MVM and MPV
- feces and urine (soiled bedding) by oronasal exposure
- direct contact
- contaminated animal products
106
Prevention and Control of MPV / MVM
- Decontamination since virus persists in environment
- Quarantine since immunocompetent mice can clear infection (MVM)
- cage-by-cage Test-and-cull (MPV)
- Rederivation and embryo transfer also paossible
107
Research concerns for MPV and MVM
- studies of immune response or mitotically active cells
- infection of animal cells or products can affect experiments
108
How long is MVM thought to last in immunocompetent hosts?
~ 3 weeks
109
Name the two polyomaviruses of mice
- Polyoma virus (PyV)
- K virus
110
What is the major viral oncogene of PyV
Middle T antigen (MT antigen)
111
T/F natural infection with polyomavirus is rare, but experimental infection has been used to induce tumors
true
112
Clinical Signs of PyV
- subclinical in natural infections of immunocompetent mice
- tumors, neuro dz, and wasting in immunodeficient mice
113
C57BL/6 are ____ to PyV, while AKR and CBA mice are ________
- resistant
- highly susceptible
114
Gross lesions of PyV
- neonatal mice and immunodeficient mice: multifocal necrosis and inflammation followed by tumor formation in numerous tissues
- immunocompetent mice: won't see much
115
Transmission of PyV
- IN (virus shed in urine, feces, and saliva); direct contact?
- Contamination of cell lines and transplantable tumors
116
prevention and control of PyV
elimination of infected mice and materials
117
Research concerns of PyV
infection of research cell lines, contamination, and spread to susceptible mice
118
tissue tropism of PyV
Polytropic - will infect many cells
- intranuclear inclusions most obvious in renal tubules and in cytolytic lesions
119
In which tissue does PyV persist for months
lung and kidneys, other sites can clear the virus
120
Types of tumors from PyV in susceptible strains
- Epithelial tumors (hair follicle origin): mammary gland, salivary gland, and thymis
- mesenchymal tumors: renal carcinomas, osteosarcomas, hemangiosarcomas, and fibrosarcomas
121
122
T/F: neonatal mice are susceptible to infection via oronasal inoculation, and you may see low mortality in initial stages
false; will see high mortality
123
Clinical disease of PyV in neonates
- runting syndrome
- polyarteritis
- enhanced autoimmune disease
124
Clinical disease of PyV in nude mice
- multisystemic wasting disease
- paralysis (infection of oligodendroglia and demyelination, or tumors of vertebrae)
125
K virus is also referred to as _____ and _____
- Kilham's virus
- Murine Pneumotropic Virus (MptV)
126
T/F K virus is oncogenic
False; it is not oncogenic
127
transmission of K virus
- oronasal
- fecal-oral
128
Which mice develop disease with K virus
- Neonatal mice (usually resistant by 12-18d of age)
- immunodeficient mice
129
What is the main viral target of K virus
- vascular endothelium
-- replicates in the intestinal capillary endothelium
-- high tissue tropism for pulmonary endothlium
130
Gross findings of K virus
- restricted to lungs
--- congestion, edema, hemorrhage, and atelectasis
131
Histopath findings of K virus
- lymphocytic interstitial pneumonia during recovery
- Can have leukocytic infiltrates in liver sinusoids and nuclear ballooning of cells lining sinusoids
- viral persistence in renal tubular epithelium
132
PyV prevalence in vivaria
rare, but commonly used in research
133
K virus prevalence in vivaria
essentially eliminated
134
PyV tissue tropism
Polytropic
lung and kidney; multi-organ tumor function
135
K virus tissue tropism
vascular endothelium
136
PyV CS in natural infection
immunodeficient mice: wasting, tumor induction, neuro signs
137
K virus CS in natural infection
none
138
PyV virus CS in experimental infection
acute dz in neonates with tumor formation in survivors
139
K virus CS in experimental infection
Dyspnea, pulmonary hemorrhage, and edema in neonates and nudes
140
Does PyV have Intranuclear inclusions?
yes
141
Does K virus have intranuclear inclusions?
yes
142
What does papillomavirus (MusPV) cause in T-cell-deficient mice
- papillomas
143
T/F murine papillomavirus is oncogenic
false, it is not
144
