The phenotype of the nude mouse model is:
Athymic and hairless (linked gene defect). ** No T cell function.**
- Defectivve transcription factor gene controlling thymic epithelial cell differentiation
Phenotype of SCID mouse?
Hypoplastic lymphoid tissues. No Ig or T cell responses. Sensitive to ionizing radiation because of defective DNA repair mechanisms.
- Defective DNA-dependent kinase that recombines gene segments coding for T (TcR) and B (Ig) cell receptors
T/F. Ectromelia virus is highly stable at room temperature.
TRUE
Which strains are most susceptible to mousepox (ectromelia) virus? Which are resistant?
Most susceptible: DBA/1, DBA/2, BALB/c, A, C3H
**Resistant: **C57BL/6, AKR
Mouse cytomegalovirus (MCMV) and thymic necrosis virus (MTV) are what type?
herpesviruses
MCMV is betaherpesvirus
Describe clinical signs and reservoir of MCMV. The pathogenicity of mouse cytomegalovirus (MCMV) __________ with age.
pathogenicity decreases with age
Asymptomatic in adult immunocompetent mice. Immunodeficient adult mice are susceptible to pathogenic infection. Neonates are highly susceptible to lethal infection, although maternal immunity is protective. Wild mice are reservoir. Persistently infected mice shed virus in saliva, urine, and tears for many months.
- Detection of enlarged cells with intranuclear inclusions, especially in salivary glands, are diagnostic
A central feature of non-lethal infection of mice with MCMV is
persistent infection (although MTV can also cause PI in salivary glands)
Persistent infection often affects the salivary glands and pancreas. Detection of enlarged cells with intranuclear inclusions, especially in salivary glands, are diagnostic, if present.
The type of immunity critical for protection against MCMV infection is
cellular
Severe, diffuse necrosis of the thymus is a clinical sign associated with
mouse thymic virus (MTV)
The hallmark histologic lesion of MTV is:
thymic necrosis associated with intranuclear herpetic inclusions in mice exposed within ~1 week after birth
MVM transmission and infection:
- Parvovirus
- transmission by oronasal exposure and viral contamination of biologicals
- excreted in feces and urine
- infects GI tract
- persistent infection not a feature, unlike MPV
Characteristics of mouse adenovirus?
- nonenveloped DNA virus
- causes intranuclear inclusions in vivo and in vitro
- MAdV-1 (FL) and MAdV-2 (K87); MAdV-2 responsible for all natural infections
- Asymptomatic in immunocompetent mice, except possible transient runting in neonates
- MAdV-1 cause multisystemic disease characterized by necrosis
- MAdV-2 causes amphphilic, intranuclear inclusions in intestinal epithelium especially in distal small intestine and cecum - pathognomonic
LAM, p 64
Histologic viral inclusions in mouse parvovirus are easier to detect in
infant mice than in adults
Mouse tissue. Etiology?
MAdV-2
The small DNA virus of mice that is highly antigenic in adults and induces multiple types of tumors in mice infected as neonates is called:
Murine polyoma virus (MPyV) - family Polyomaviridae (the other is K virus)
Natural infection is rare and asymptomatic in immunocompetent mice. Primary importance stems from use in murine models of experimental oncogenesis.
- Experimental inoculation of neonatal mice can produce viremia, and acute death. Surviving mice develop tumors 2-12 months later.
- Salivary glands are common sites for tumor development. Also, skin adnexa, upper GI, and kidneys
- Athymic mice can develop cytolytic and inflammatory lesions, followed by multisystemic tumor formation. IN inclusions may be present in cytolytic lesions.
When and where do tumors arise in neonates experimentally infected with polyoma virus?
Experimental infection of neonatal mice can produce viremia and acute death. In surviving mice, tumors appear 2-12 months post-inoculation, and the salivary glands are prevalent sites in most strains. Tumors can also appear in skin adnexa, upper GI, and kidneys.
T/F. Prevention measures for airborne transmission are required for polyoma virus
True
Describe lactate dehydrogenase elevating virus (LDV) in terms of taxonomy, transmission, and clinical signs.
togavirus specific to mice
Primary mouse-to-mouse transmission is mechanical transfer from aggressive behavior. Inoculation of mice with contaminated biologicals (cell lines, transplantable tumors, serum) is most common source of induced infection. LDV can infect, but not replicate, in tumor cells.
Asymptomatic usually. Mild leptomeningitis and myelitis in C57BL/6. Causes increased levels of several serum enzymes, most notably lactate dehydrogenase (LDH). SJL/L mice show most dramatic increases (15-20X normal), which is due to a recessive somatic gene)
Infections with LDV induces a duration of viremia that peaks at _____ and then is __________
12-24 hours after infection; persistent at a lower level lifelong
Why is LDV difficult to detect?
infection produces modest humoral response, but virus-antibody complexes interfere with serologic tests
inhibitory factors in cells and serum may cause false negative PCR
Lungs from an immunocompetent mouse that exhibited generalized signs of illness in addition to chattering. What is the most likely etiology and mouse strain?
Sendai virus
DBA/2 are highly susceptible to lethal infection.
- Paramyxoviridae, genus Repirovirus, related to parainfluenza 1 of humans
- Recent studies have shown that SV and parainfluenza 1 replicate equally well in URT of African greens and chimps
- SV also infectious to laboratory rats and hamsters. Guinea pigs can be experimentallt infected
P&B, p 37
What is your presumptive diagnosis for 2-week old mice presenting with oily, matted hair, emaciation, and jaundice?
Reovirus-3
- Histologic evidence of multisystemic necrosis is also consistent with Reovirus-3
- Should be confirmed by immunohistochemistry or virus isolation
- Differential for diarrheal disease of infant mice: mouse coronavirus, EDIM, Salmonella, C. piliforme
LAM, p 73
Why does EDIM cause more severe disease in mice less than 2 weeks old?
Rotavirus preferentially infects terminally differentiated enterocytes of the small and large intestine. The number of such cells decreases as the intestinal tract matures.
- Note clubbing of intestinal villi with cytoplasmic swelling and vacuolization
LAM, p 73-4
Phenotype of Rag-1 and Rag-2?
Hypoplastic lymphoid tissue. No Ig or T cell responses.
- Defective recombinase enzymes (Rag-1 or Rag-2), preventing formation of functional B alpha (Ig) and T (TcR) cell receptors
Phenotype of XID?
Decreased B cell numbers, low IgM. Impaired response to polysaccharide antigens.
- Defect in Bruton’s tyrosine kinase gene affecting signal transduction in B cells
- Model for human X-linked agammaglobulinemia
Phenotype of Moth-eaten mouse?
Deficient humoral and cellular immunity. Lack cytotoxic T and NK cells. Moth-eathen pelage secondary to folliculitis. Autoimmune syndromes. Hypergammaglobulinemia.
- Defective phosphatase, impairing signal transduction from cell receptors
- Research use in autoimmune syndromes, and apoptosis studies
Phenotype of Beige mouse?
Diluted coat color. Lysosomal storage disease. Impaired chemotaxis, bactericidal activity of neutrophils, decreased NK activity.
- Mutation on chromosome 13 affects pigment granules (coat, retina) and lysosomal granules of type II pneumocytes, mast cells, and NK cells
What is this, and what mouse strains did it most likely come from?
“Mosaic” spleen from necrosis and scarring of red and white pulp, characteristic of mousepox infection in susceptible strains.
Immunodeficient strains, and DBA/1, DBA/2, BALB/c, A, and C3H are most susceptible to lethal infection.
What vaccination does this represent? What is a positive and negative reaction and what does it mean?
This is a positive “take” in a mouse that vaccinated with the hemagglutanin-deficient strain of vaccinia virus (IHD-T) by scarrifying skin on dorsum of tail. A “take” occurs in 6-10 days, and means that the mouse is uninfected. Negative reaction (no take) occurs when mice are presently infected with mousepox. Vaccination controls or prevents clinically apparent mousepox.
- Vaccinia virus is a human pathogen
What kind of virus is ectromelia virus?
orthopoxvirus
named from the greek ectro (amputation) and melia (limb) based on clinical presentation
Rate these mouse strains based on susceptibility to mousepox virus (highly susceptible, moderately susceptible, or highly resistant)
A
AKR
BALB/c
BC
C3H/He
CBA
C56BL/6
DBA/1
DBA/2
SJL
Highly Resistant: C56Bl/6
Moderately Susceptible: AKR, SJL
Highly Suseptible: A
BALB/c
BC
C3H/He
CBA
DBA/1
DBA/2
Clinical signs of ectromelia virus
sudden death, ruffle fur, prostration, focal or generalized rash anywhere on the body (poxes), necrosis and amputation of feet and tail.
Epizootiology of mousepox
uncommon; direct contact - skin invasion
virus highly stable at dry, room temperature
infant and aged mice most susceptible
Pathology of ectromelia virus
intracytoplasmic inclusion bodies in the epithelium (Type A or Marchal IB)
hepatocellular necrosis (white spots on liver)
splenic necrosis and scarring of red and white pulp (mosaic pattern)
DDX for white spots on the liver
ectromelia
Tyzzer’s disease
mouse hepatitis virus
DDX for high morbidity and high mortality
ectromelia, Tyzzers’ disease, mouse hepatitis virus, Sendai pneumonia
Describe IHD-T in prevention of mousepox
Hemagglutinin-deficient vaccinia virus is used to scarify the skin on the dorsum of the tail. previously uninfected mice take the procedure, whereas mousepox infected mice do not. vaccination may still lead to transient infection. vaccinia virus may be shed from take sites (zoonotic)
Etiology of mouse cytomegalovirus
betaherpesvirus (one of two herpes viruses that mice are naturally susceptible to)
Clinical signs of MCMV
clinically silent usually, but experimental inoculation of neonates can cause lethal disease due to multisystemic necrosis and inflammation.
Diagnosis of MCMV
Serology
PCR
Weak humoral response - cellular immunity more important
Histopathology of MCMV
large cells with INIBs, ICIBs, lymphoplasmacytic interstitial inflammation of the cervical salivary glands
DDX for MCMV
MTV - produces thymic nercosis but infects salivary glands too
Polyoma virus - can produce sialodenitis with IBs
Etiology of MTV
Mouse Thymic Virus - herpesvirus (murid herpesvirus 3)
Clinical signs of MTV
subclinical but transiently suppreses immunity
Epizootiology of MTV
Low prevalence
infection at any age
lesions only in perinatally infected mice
persistent infections in infants and adults
transmission through saliva
Pathology of MTV
severe, diffuse thymic and lympoid necrosis in mice infected around birth
Primary cellular tropism of MTV
CD4+ cells
Diagnosis of MTV
Thymic necrosis with INIBs
PCR
DDX for MTV
Thymic lesions - sever coronavirus infection (but EDIM is associated with diarrhea)
Etiology of MVM
Minute Virus of Mice - parvovirus
How is MVM serologically differentiated from MPV?
viral capsid proteins
Clinical signs of MVM
subclinical, but affects gorwth of transplantable neoplasms
Epizootiology of MVM
Persists in the environment
oronasal exposure
transient infections (less than 3 weeks)
Pathology of MVM
Nonpathogenic in immunocompetent adult mice
infection in SCID, B-cell deficient mice results in lethal damage to granulomacrophagic, megakaryocytic, and erythrocytic hematopoietic tissue with severe leukopenia
Diagnosis of MVM
Serology
PCR
Epizootiology of MPV
persistent infections
tropism for intestinal crypts and lymphoid organs
shedding for about 3 weeks, depending on strain of mouse
Clinical signs of MAV-1 vs. MAV-2
MAV-1: experimental inoculation in infant mice causes severe disease - scruffiness, lethargy, runting, death; can cause wasting disease an athymic mice
MAV-2: natural infection in immunocompetent mice is subclinical; virus is enterotropic; transient runting in infant mice
Epizootiology of MAV
Transmission by ingestion
persistent infection in experimentally infected adults with MAV-1
transient infection in experimentally infected adults with MAV-2
Pathololgy of MAV-1
multisystemic necrosis with INIB in infant mice
Immunocompetent mice subclinical w/ seroconversion
immunocompromised mice can develop inestinal hemorrhage and wasting
Pathology of MAV-2
amphophilic intestinal INIB
Types of Polyomaviridae
Polyoma virus (PyV)
K-virus
Clinical signs of K virus
subclinical in immunocompetent adults
immunocomprimised adults and neonatal mice get pulmonary hemorrhage and edema
persistent shedding
Clinical signs of PyV
subclinical in immunocompetent mice
immunodifficent mice get tumors, neurological disease, wasting
Epizootiology of PyV
infection from contaminated tumors
natural transmission via respiratory route
persistent infection in neonates and immunodeficient adults
transient infection in adults
Most resistant and susceptible mouse strains to Pyv tumor oncogenesis
B6 - most resistant
Most susceptible - AKR, C3H, C58, CBA, SWR
Pathology of PyV
Epithelial and mesenchymal tumors in multiple organs of mice surviving inoculation
Etiology of LDV
Lactate dehydrogenase-elevating virus, Arteriviridae, enveloped, RNA virus
Clinical signs of LDV
usually subclinical
elevated LDH levels, as well as other serum enzymes
poliomyelitis in immuosupressed mice
Epizootiology of LDV
mechanical transfer - wounds, bites
contaminated biologic material
lifelong viremia
Pathology of LDV
viral interference with reticuloendothelial clearance of LDH
selective targeting of F4/F8 + macrophages
poliomyelitis requires immunosuppression, suscptible strain, endogenous ecotropic MLV
Diagnosis of LDV
Elevation of LDH-V isoenzyme 10-20x normal
PCR
Etiology of LCMV
Arenaviridae, enveloped RNA virus
Clinical signs of LCMV
aged mice lose weight and die
immune mediated lymphocytic choriomeningitis with experimental infection
Epizootiology of LCMV
wide distribution, natural infection in rodents and NHPs
mouse and hamster transmit infection to each other and to other animals
horizontal and vertical transmission
Pathology of LCMV
IC inoculation: nonsuppurative leptomeningitis, choroiditis, and focal perivascular lymphocytic infiltrates
Liver lesions can include hepatocyte necrosis accompanied by nodular infiltrates of lymphoid cells and Kupffer cells, activated sinusoidal endothelium, an occasional granulocyte or megakaryocyte, and fatty metamorphosis
In adult mice with acute LCMV infection, virus multiplies in all but which cells?
a. Dendritic cells
b. B cells
c. macrophages
d. T cells
d. T cells