Mouse Pathology Review - RNA Viruses Flashcards
(111 cards)
1
Q
What is the clin path abnormality associated with Lactate dehydrogenase-elevating virus (LDV)
A
elevation of LDH (specifically, LDH-V)
2
Q
LDV is typically ____, but _____ has occurred with ______ C58 and AKR mice inoculated with LDV
A
- subclinical
- poliomyelitis
- immunosuppressed
3
Q
Transmission of LDV
A
- mechanical transfer from bite wounds - results in lifelong viremia
- inoculation of mice with contaminated animal products (cell lines, transplantable tumors, or serum) is probably most common source of induced infection
4
Q
Sources of LDV infection
A
- wild mice
- transplantable tumors
- hybridomas
5
Q
Detection of LDV
A
- PCR is a preferred diagnostic.
- LDH enzyme assays are often false positives
6
Q
Prevention of LDV
A
- Monitor cell lines that tumors are being transplanted from
- Keep wild mice away from colonies
7
Q
Research complications of LDV
A
- adverse effects on immunological studies
— reduced antibody production, transient thymic necrosis, lymphopenia, suppression of cell-mediated immune response, and enhance/suppress tumor grwoth
8
Q
LDV infection is subclinical except for ____ and ____, and results in a _____
A
- Immunosuppressed C58 mice
- Inoculated AKR mice and ICR-scid mice
- paralytic syndrome
9
Q
Why is LCMV considered a significant pathogen?
A
It’s Zoonotic, and causes symptoms of meningitis in humans
10
Q
What is LCMV
A
Lymphocytic choriomeningitis virus
11
Q
What is the natural reservoir host of LCMV
A
wild mice
12
Q
Which animal is not naturally infected with LCMV?
A
the Rat
13
Q
What is the amplifying host of LCMV?
A
hamsters
14
Q
What ABSL level should be followed when working LCMV-infected hamsters?
A
ABSL 3
15
Q
What ABSL level should be followed when working with LCMV-infected mice?
A
ABSL 2
16
Q
What is the primary source of LCMV in humans?
A
hamsters
17
Q
Transmission of LCMV
A
- via aerosol and direct contact
- nasal secretions
- urine
- saliva
18
Q
What is the typical infection mode of Immunocompetent adult lab mice with LCMV
A
Adult mouse inoculated with virus-infected biologicals -> self-limiting and subclinical disease -> clearance of virus -> now a persistently infected mouse
19
Q
Explain what “Late disease” is in regards to LCMV
A
Pups infected in utero or as neonates are immune tolerant of LCMV, but that immune tolerance is very specific to LCMV. Mice develop antibodies to other pathogens. Immune tolerance breaks down late in life (after breeding age) and the mice lose weight and die. In utero infection can cause low level loss of fetal mortality and cannibalism of infected pups. Infection of older pups can result in viral clearance or death
20
Q
What may be seen with LCMV “late disease?”
A
Lesions are characterized by formation of immune complexes and associated inflammation. Renal glomeruli and choroid plexus are most severely affected
21
Q
What happens with intracerebral inoculation of LCMV in immunocompetent mice
A
- an immune-mediated lymphocytic choriomeningitis develops 5-6 days post-inoculation -> May see sudden death or any of the following: ruffled fur, hunched appearance, motionless, neuro deficits (tremors when suspended by tail (and sometimes spontaneously), colonic convulsions, rear leg extensions) -> death or recovery in several days
22
Q
What happens with peripheral inoculation with viscerotrophic strain of LCMV in immunocompetent mice
A
- subclinical
or - result in clinical signs (ruffled fur, conjunctivitis, ascites, somnolescence, and death). -> if mice survive, recovery may take weeks. Those that survive may have immune exhaustion due to lymphodepletion.
23
Q
Diagnosis of LCMV
A
- Serology of immunocompetent mice (carrier mice may have false negatives)
- PCR on biologic products and cell lines
- Sentinel testing
- Histology
24
Q
What are the four forms of LCMV
A
- Natural infection, self-limiting and subclinical in immunocompetent mice
- “late disease” (L) - late-onset disease w/ immune complex glomerulonephritis in previously asymptomatic carriers (9-12mos. old)
- Intracerebral inoculation (C) - ass. w/ neurotropic or cerebral form include sudden death (M for mortality) 5-6 days after inoculation
- “Visceral form” (V) - results from peripheral inoculation w/ viscerotropic strains - may be asymptomatic or have nonspecific signs
25
What is the pneumonic for LCMV
L - "LATE disease"
C - "IntraCEREBRAL inoculation"
M - "MORTALITY and runting in neonates"
V - "VISCERAL form in adults inoculated with 'viscerotropic strain'"
26
Which mouse silently harbors LCMV?
Nude mouse
- LCMV multiples in DCs, B cell, and macrophages; T-cells are resistant
- Virus elimination and virus-associated immune injury are T-cell mediated. Athymic nude mice don't have T cells or B cells
27
Research implications of LCMV
- sick mice
- Reduced reproductive efficiency
- Deaths in colony
- Contaminant of biological product derived from mice
- ZOONOTIC
28
Prevention and control of LCMV
- adequate testing of animals and animal products are the best way to prevent entry. Euthanize all hamsters and immunodeficient mice that test positive
Test and cull, depopulation
29
Differentials of LCMV
- Mouse hepatitis virus
- Mouse Encephalomyelitis virus
- Meningoencephalitis from bacterial infections
- Toxins
- Trauma
- Neoplasia
30
What are the two viruses of the Paramyxoviridae family that infect mice?
- Sendai Virus
- Pneumonia Virus of Mice (PVM)
31
Prevalence of SV in Vivaria / contagion
- rare to absent
- Very contagious!
32
Prevalence of PVM in vivaria / contagion
- Declining
- not very contagious
33
Species susceptible to SV
Mice, rats, hamsters, Guinea pigs
34
Species susceptible to PVM
mice, rats, hamsters, other rodents +/- rabbits
35
Clinical signs due to natural infection of SV in immunocompetent animals
- Chattering, dyspnea, hunched posture, weight loss, ocular crusting, death.
- Neonates commonly die (lethal infection)
36
Clinical signs due to natural infection of PVM in immunocompetent animals
Subclinical
37
SV tissue tropism
- respiratory epithelium
- *** Type II pneumocytes
38
PVM tissue tropism
Respiratory tract
39
Does SV cause wasting in nude mice?
yes
40
Does PVM cause wasting in nude mice?
yes
41
Gross lesions of SV in immunocompetent animals
- partial to complete consolidation of the lungs
- Bronchointerstitial pneumonia with atelectasis, centered on lung hilus
- 2° bacterial infections resulting in bronchopneumonia
42
Gross lesions of PVM in immunocompetent animals
none!
43
Susceptibility to SV varies by mous strain and results from difference in _____ _____ function.
mucociliary apparatus
44
Mice strains susceptible to SV
- DBA/2
45
Mice strains resistant to SV
- C57BL/6
46
Immune compromised mice take longer to show clinical signs because ____ of the respiratory epithelium is _____
- destruction
- immune-mediated
47
Histopath lesions associated with SV infection
- Hypertrophy and hyperplasia of bronchiolar epithelium
48
What are the two reoviruses of importance in mice
- Reovirus 3
- Rotavirus A (EDIM)
49
What is another name for Rotavirus A
Epizootic diarrhea of infant mice (EDIM) virus
50
Transmission of SV
Aerosol, highly contagious
51
Detection of SV
- Serology
- sentinel testings
- confirm with histopath / IHC
52
DDX of SV
- PVM
- respiratory mycoplasmosis or other bacterial pneumonia (could be secondary)
53
Which reovirus is associated with a naturally occurring infection
Reovirus 3
54
What does REO stand for in reovirus
Respiratory Enteric Orphan - virus
55
Prevalence in vivaria / contagion of Reovirus 3
rare / contagious only in pups <2 weeks old
56
Prevalence in vivaria / contagion of EDIM
common / highly contagious
57
Clinical signs in natural infection of Reovirus 3 immunocompetent mice
- Runted pups, EMACIATION, icterus, neuro signs, diarrhea, fatty feces
- subclinical in adults
58
Clinical signs of natural infection EDIM in of immunocompetent mice
Runted pups THAT STILL NURSE, diarrhea, fatty feces, can die of obstipation
59
Tissue tropism of Reovirus 3
M cells of Peyer's patches -> multiple tissues
60
Tissue tropism of EDIM
terminally differentiated enterocytes only
61
Reovirus 3 strain susceptibility
no strain predominance
62
EDIM strain susceptibility
- BALB/c susceptible
- C57BL/6 resistant
63
Transmission of Reovirus 3
- direct contact among infant mice, tumor implantation, injection
- transmission is inefficient among adult mice
64
Gross lesions of Reovirus3
- Acute disease: large and dark livers w/ yellow foci of necrosis, red and distended intestines (w/ bright yellow intestinal contents in infants)
65
Histopath of reovirus 3
necrosis and inflammation or many organs (brain, heart, salivary glands, lymph nodes)
***the most significant microscopic lesion is ACUTE DIFFUSE ENCEPHALITIS that has a vascular distribution***
66
EDIM is caused by _____ and is limited to mice _____ of age
- rotavirus A
- < 2 weeks of age
67
Clinical signs of EDIM and gross lesions of EDIM
- diarrhea, steatorrhea, fluid-dilated small intestine, runting
PRESENCE OF MILK SPOT indicates still eating, helpful to differentiate from reovirus 3 and LIVIM
68
What does the milk spot indicate for mice infected with EDIM
they still have an appetite
69
Histopath of EDIM
vacuolation of the enterocytes on the villus tips (bc it can only replication in terminally differentiated enterocytes)
Villi will have a clubbed appearance due to this pathology
70
susceptibility of EDIM
BALB/c more susceptible than C57BL/6
71
What are the two biotypes of Murine hepatitis virus
- Enterotropic: tropism for enterocytes (of intestinal tract)
- Polytropic: tropism for upper respiratory mucosa (but has multisystemic dissemination)
72
How can you differentiate MHV from EDIM
EDIM infected mice will have a milk spot, MHV won't
73
What is another name for murine hepatitis virus
Lehtal intestinal virus of infant mice (LIVIM)
74
Clinical signs of MHV
- pup will have inappetence, diarrhea, dehydration, and likely death
75
Transmission of MHV
- natural transmission via respiratory and oral routes
- contaminated biologicals
76
Which mouse, if infected with the polytropic strain of MHV, may develop a wasting syndrome with progressive paralysis?
athymic nude mice
B and T cells are required to clear the virus, therefore immunodeficient mice cannot clear infection and may die acutely or develop a wasting syndrome
77
T/F the Enterotropic strain of MHV causes minimal disease in nude or SCID adults
true
78
Gross lesion of MHV
liver with yellow/white foci (necrosis)
79
what is the hallmark sign of MHV infection?
syncytia
- may be transient in immunocompetent strains, will be a persistent feature in chronically infected, immunodeficient mice
80
Age impacted by enterotropic MHV
all ages
81
age impacted by polytropic MHV
neonates < 2 weeks old
82
strains impacted by enterotropic MHV
all strains
83
strains impacted by polytropic MHV
immunocompromised strains
84
tissue tropism of enterotropic MHV
intestines
85
tissue tropism of polytropic MHV
upper respiratory mucosa (with multisystemic dissemination)
86
clinical signs of enterotropic MHV
empty stomach, dehydrated, runted neonates
87
clinical signs of polytropic MHV
subclinical infection after weaning, can have CNS signs
88
pathology of enterotropic MHV
necrotizing enterotyplocolitis w/ mortality in neonates
89
pathology of polytropic MHV
- syncytia
- yellow, white foci (necrosis) in multiple tissues, liver (classical lesion: white spotty liver
90
Diagnosis of MHV
- serology is most reliable diagnostic
- Sentinels key to continued serological surveillance
- Fecal PCR also available
91
What are some differentials for diarrheal illness, runting or death in suckling and wasting in immunodeficient mice
- MHV
- EDIM
- mousepox (ECTV)
- Reovirus 3
- Tyzzer's disease
- salmonellosis
- Adenovirus
- Helicobacter hepaticas
92
DDx for neurologic signs
- MHV
- Mouse encephalomyelitis virus
- Neoplasia, including Polyoma virus-induced tumors in athymic mice
93
T/F maternal antibodies provide passive immunity to pups
True
94
Theiler's Murine Encephalomyelitis virus (TMEV) replicates in which intestines? what lesions are present?
- within the intestines
- no intestinal lesions are present
95
What are the clinical signs / gross lesions of TMEV?
- flaccid posterior paralysis (poliomyelitis phase)
- death due to inability to obtain food/water
- exceedingly rare in immunocompetent mice
96
Histopath lesions of TMEV
neuronlysis, nonsuppurative meningitis, and perivasculitis from spinal cord
97
Tropism of Murine norovirus (MNV)
macrophages and dendritic cells
98
Research concerns for MNV
may interfere with enteric disease studies
99
Clinical signs of MNV in immunocompetent mice
none
100
Detection of MNV
- Serology
- PCR
101
How can MNV be eliminated from a colony?
- depopulate and decontaminate
- rederive
- cross-foster
102
Why is test and culling not useful in MNV outbreaks?
MNV persists in environment
103
Best option for routine screening of MNV
sentinel testing -- Mesenteric LN PCR testing postmortem bc of tropism for macrophages and dendritic cells
104
What other diseases can mesenteric lymph node testing be used for?
- MPV, MVM, MHV, and salmonella
105
Biggest concern regarding hantavirus
It is zoonotic
106
how does hantavirus differ from other Bunyaviridae viruses?
no arthropod transmission
107
Transmission of Hantavirus
- urine, fecal oral, saliva (?)
108
Natural reservoir of hantavirus in the wild
the Norway Rat (Rattus norvegicus)
109
What are the two syndromes of Hantavirus in people?
- Hemorrhagic fever with renal syndrome (HFRS)
- Hantavirus pulmonary syndrome
LIFELONG INFECTION
110
Testing and diagnosis of PCR
- Serology and PCR
111
Clinical signs of Hantavirus
infection is subclinical
