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1

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

 

 

2

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

 

3

T/F.  Ectromelia virus is highly stable at room temperature.

 

TRUE

 

4

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

 

 

5

Mouse cytomegalovirus (MCMV) and thymic necrosis virus (MTV) are what type?

 

 

 

herpesviruses

MCMV is betaherpesvirus

 

 

 

6

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

 

 

7

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.

 

 

 

 

8

The type of immunity critical for protection against MCMV infection is

 

 

cellular

 

9

Severe, diffuse necrosis of the thymus is a clinical sign associated with

 

 

mouse thymic virus (MTV)

 

10

The hallmark histologic lesion of MTV is:

 

 

 

 

thymic necrosis associated with intranuclear herpetic inclusions in mice exposed within ~1 week after birth

 

 

 

11

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

 

12

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

 

13

Histologic viral inclusions in mouse parvovirus are easier to detect in

 

 

 infant mice than in adults

 

14

Mouse tissue.  Etiology?

 

MAdV-2

 

15

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.

 

 

16

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.

 

17

T/F.  Prevention measures for airborne transmission are required for polyoma virus

 

 

True

 

18

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)

 

19

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

 

20

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

 

21

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

 

22

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

 

23

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

 

24

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

25

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

26

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

27

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

28

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.

29

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 

30

What kind of virus is ectromelia virus?

orthopoxvirus

named from the greek ectro (amputation) and melia (limb) based on clinical presentation

31

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

32

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.

33

Epizootiology of mousepox

uncommon; direct contact - skin invasion

virus highly stable at dry, room temperature

infant and aged mice most susceptible

34

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)

35

DDX for white spots on the liver

ectromelia

Tyzzer's disease

mouse hepatitis virus

36

DDX for high morbidity and high mortality

ectromelia, Tyzzers' disease, mouse hepatitis virus, Sendai pneumonia

37

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)

38

Etiology of mouse cytomegalovirus

betaherpesvirus (one of two herpes viruses that mice are naturally susceptible to)

39

Clinical signs of MCMV

clinically silent usually, but experimental inoculation of neonates can cause lethal disease due to multisystemic necrosis and inflammation.

40

Diagnosis of MCMV

Serology

PCR

Weak humoral response - cellular immunity more important

41

Histopathology of MCMV

large cells with INIBs, ICIBs, lymphoplasmacytic interstitial inflammation of the cervical salivary glands

42

DDX for MCMV

MTV - produces thymic nercosis but infects salivary glands too

Polyoma virus - can produce sialodenitis with IBs

43

Etiology of MTV

Mouse Thymic Virus - herpesvirus (murid herpesvirus 3)

44

Clinical signs of MTV

subclinical but transiently suppreses immunity

45

Epizootiology of MTV

Low prevalence

infection at any age

lesions only in perinatally infected mice

persistent infections in infants and adults

transmission through saliva

46

Pathology of MTV

severe, diffuse thymic and lympoid necrosis in mice infected around birth

47

Primary cellular tropism of MTV

CD4+ cells

48

Diagnosis of MTV

Thymic necrosis with INIBs

PCR

49

DDX for MTV

Thymic lesions - sever coronavirus infection (but EDIM is associated with diarrhea)

50

Etiology of MVM

Minute Virus of Mice - parvovirus

51

How is MVM serologically differentiated from MPV?

viral capsid proteins

52

Clinical signs of MVM

subclinical, but affects gorwth of transplantable neoplasms

53

Epizootiology of MVM

Persists in the environment

oronasal exposure

transient infections (less than 3 weeks)

54

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

55

Diagnosis of MVM

Serology

PCR

56

Epizootiology of MPV

persistent infections

tropism for intestinal crypts and lymphoid organs

shedding for about 3 weeks, depending on strain of mouse

57

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

58

Epizootiology of MAV

Transmission by ingestion

persistent infection in experimentally infected adults with MAV-1

transient infection in experimentally infected adults with MAV-2

 

59

Pathololgy of MAV-1

multisystemic necrosis with INIB in infant mice

Immunocompetent mice subclinical w/ seroconversion

immunocompromised mice can develop inestinal hemorrhage and wasting

 

60

Pathology of MAV-2

amphophilic intestinal INIB

61

Types of Polyomaviridae

Polyoma virus (PyV)

K-virus

62

Clinical signs of K virus

subclinical in immunocompetent adults

immunocomprimised adults and neonatal mice get pulmonary hemorrhage and edema

persistent shedding

63

Clinical signs of PyV

subclinical in immunocompetent mice

immunodifficent mice get tumors, neurological disease, wasting

64

Epizootiology of PyV

infection from contaminated tumors

natural transmission via respiratory route

persistent infection in neonates and immunodeficient adults

transient infection in adults

65

Most resistant and susceptible mouse strains to Pyv tumor oncogenesis

B6 - most resistant

Most susceptible - AKR, C3H, C58, CBA, SWR

66

Pathology of PyV

Epithelial and mesenchymal tumors in multiple organs of mice surviving inoculation

 

67

Etiology of LDV

Lactate dehydrogenase-elevating virus, Arteriviridae, enveloped, RNA virus

68

Clinical signs of LDV

usually subclinical

elevated LDH levels, as well as other serum enzymes

poliomyelitis in immuosupressed mice

69

Epizootiology of LDV

mechanical transfer - wounds, bites

contaminated biologic material

lifelong viremia

70

Pathology of LDV

viral interference with reticuloendothelial clearance of LDH

selective targeting of F4/F8 + macrophages

poliomyelitis requires immunosuppression, suscptible strain, endogenous ecotropic MLV

71

Diagnosis of LDV

Elevation of LDH-V isoenzyme 10-20x normal

PCR

 

 

72

Etiology of LCMV

Arenaviridae, enveloped RNA virus

73

Clinical signs of LCMV

aged mice lose weight and die

immune mediated lymphocytic choriomeningitis with experimental infection

74

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

 

 

75

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

76

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