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1. Que. Lymphocytic choriomeningitis virus (LCMV) carrier mice usually develop as a result of asymptomatic prenatal or neonatal infection, which induces tolerance to the virus. Such mice can have persistently high concentrations of virus in many organs, thereby facilitating virus excretion in __________, __________, and __________.
Ans. saliva, nasal secretions, and urine, p.67
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2. Que. Mice can transmit LCMV to __________, which can remain viremic and viruric for many months even if they contract infection as adults.
Ans. hamsters, p.67
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3. Que. The primary laboratory animal species that is the primary source of human LCMV infection is the __________.
Ans. hamster (infected mice are not a significant source of human exposure), p.67
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4. Que. LCMV disease in mice is a prototype for virus-induced, _______________ and for immune complex disease.
Ans. T-lymphocyte-mediated immune injury, p.67
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5. Que. __________ inoculation of LCMV into immunocompetent adult mice can induce nonsuppurative leptomeningitis, choroiditis, and focal perivascular lymphocytic infiltrates.
Ans. Intracerebral, p.67
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6. Que. Pick the terms that correctly complete this sentence: In adult mice with acute LCMV infection, virus multiplies in B cells/T cells and macrophages, whereas B cells/T cells are resistant.
Ans. Multiplies in B cells; T cells are resistant, p. 68
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7. Que. Pick the terms that correctly complete this sentence: Regarding LCMV infection in mice, internal viral epitopes induce humoral/cell-mediated responses, but surface epitopes elicit humoral/cell-mediated immunity and neutralizing antibodies.
Ans. Humoral; cell-mediated, p. 68
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8. Que. True or false: elimination of LCMV virus and virus-associated immunological injury in mice are both T cell-mediated.
Ans. True, p. 68
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9. Que. At the cellular level, what causes the lesions of LCMV infection in mice?
Ans. Lesions of LCMV infection appear to develop from direct T cell-mediated damage to virus-infected cells and may involve humoral factors released from immune effector T cells., p. 68
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10. Que. True or false: LCMV can suppress humoral and cellular immunity in acutely infected mice.
Ans. True, p. 68
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11. Que. Persistent infection of LCMV in mice commonly evolves from exposure: 1) early in pregnancy; 2) late in gestation; 3) during the post-partum phase prior to weaning.
Ans. 1) early in pregnancy, p. 68
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12. Que. Pick the term that correctly complete this sentence: Prenatal or neonatal LCMV infection in mice induces immunological tolerance/frank morbidity/death.
- Ans. Immunological tolerance; LCMV can then replicate to high titer in many tissues
- , p. 68
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13. Que. True or false: persistently infected mice with LCMV develop a cell-mediated immunity to the virus,
Ans. False: persistently infected mice develop humoral immunity to LCMV., p. 68
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14. Que. What is considered a useful husbandry strategy for detecting LCMV infection in mice by seroconversion?
Ans. Using adult contact sentinel mice, p. 68
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15. Que. Intracerebral inoculation of LCMV-positive tissues should elicit neurological signs in adult mice within __________ days.
Ans. 10, p. 68
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16. Que. True or false: Intracerebral inoculation of LCMV-positive tissues into neonatal mice will produce death within 3-4 days, thereby confirming LCMV presence.
Ans. False; neonatal mice will remain asymptomatic., p. 68
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17. Que. True or false: LCMV has zoonotic potential.
- Ans. True; LCMV can be transmitted to humans, who can contract severe CNS disease. More frequently human infection resembles influenza or is asymptomatic.
- , p. 68
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18. Que. What other differential diagnoses must be considered when working up a mouse with neurologic signs that is suspected of having LCMV?
Ans. Mouse hepatitis virus; mouse encephalomyelitis virus; and meningoencephalitis from metastatic bacterial infection., p. 68
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19. Que. True or false: mouse-to-mouse spread of LCMV is rapid and complete depopulation is the only known method of control in an infected colony.
Ans. False: because mouse-to-mouse spread is slow, selective testing and culling for seropositive or carrier mice is possible. If mice are easily replaced, depopulation is a safer and more reliable option., p. 68
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20. Que. If both hamsters and mice are being used to study LCMV, explain why these two species should not be housed together (in the same room).
Ans. Infected hamsters secrete large quantities of the virus; exposed hamsters should be destroyed., p. 68
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21. Que. What family of viruses does Sendai virus belong and to which human virus is it antigenically related.
Ans. Paramyxovirus, human parainfluenza virus l., p 69.
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22. Que. Sendai viral replication during natural infection in mice is restricted to which system and which cell types.
Ans. respiratory tract, airway epithelium and type II pneumocytes., pg 69.
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23. Que. Which of the following lesions is characteristically seen with Sendai virus infection ?
- multinucleated syncytia
- squamous metaplasia of bronchial epithelium
- adenomatoid appearance of terminal bronchioles
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24. Que. What components of the inflammatory response system are responsible for both the lesions seen and recovery from Sendai virus infection ?
cellular immunity
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25. Que. Which of the following tissues are most reliable for virus isolation with suspect Sendai viral infections?
- nasopharyngeal washings
- lung tissue homogenates
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26. Que. What is the time frame recommended by the BBII to quarantine mice from introducing new (na�ve) mice into a colony in an effort to �burn out� self limiting disease from Sendai virus?
Ans. 4-6 weeks, p71
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27. Que. List the research complications from Sendai virus infection.
Ans. immunosuppression, inhibition of transplantable tumors, pulmonary changes and, breeding difficulties, p71
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28. Que. What type (DNA or RNA) of virus is Pneumonia virus of mice (PVM)?
Ans. enveloped RNA, p71
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29. Que. Name the family and genus of PVM.
Ans. family: Paramyxoviridae genus: Pneumovirus, p71
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30. Que. In what type of cells does PVM virus replicate in vitro?
Ans. BHK-cells, p71
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31. Que. What is the usual clinical presentation for natural PVM infection?
Ans. asymptomatic, p71
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32. Que. Which species does natural infection occur?
Ans. mice, rats, hamsters (probably other rodents and maybe rabbits), p71
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33. Que. PVM replicates exclusively in the __________ and reaches peak titers in __________.
Ans. respiratory tract and 6-8 days, p71
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34. Que. PVM histological lesions consist of __________, __________ and __________ ; the predominant inflammatory cell infiltrate is __________.
Ans. necrotizing rhinitis, necrotizing bronchiolitis, and interstitial pneumonia; mononuclear cells, p71
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35. Que. What diagnostic technique is the best method to separate PVM infection from other respiratory infections?
Ans. serology, p71
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36. Que. What relationship can Pneumonia Virus of Mice have with Pneomocystis carinii infection in immunodeficient mice?
Ans. PVM may coexist and exacerbate P. carinii infection., p72
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37. Que. Two members of the family Reoviridae infect laboratory mice. Name them.
- Ans. Reovirus and murine rotavirus (aka epizootic diarrhea of infant mice virus)
- , p72
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38. Que. What is significant about clinical disease caused by reovirus in mice?
Ans. Clinical disease is rare and age dependent., p72
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39. Que. ____________ and ____________ tests have been developed for the serological detection of reovirus 3 infection.
Ans. ELISA and IFA, p73
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40. Que. Rotavirus (EDIM virus) is a __________- stranded, segmented _________ virus
Ans. Double, RNA, p73
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41. Que. Clinical signs of rotavirus infection occur in mice less than ________ weeks old.
Ans. Two, p73
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42. Que. Rotavirus infection in infant mice has ____(high/low) morbidity and ______ (high/ low ) mortality.
Ans. High, low, p73
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43. Que. Rotavirus preferentially infects ________________ in the small and large intestine.
Ans. Terminally differentiated enterocytes, p73
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44. Que. Rotavirus infection is detected serologically by _______ or _______
Ans. IFA or ELISA, p73
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45. Que. EDIM virus infection must be differentiated from other intestinal disease of neonatal mice such as ______________
Ans. Corona virus, MHV, Reovirus, Tyzzer�s disease, Salmonellosis ., p74
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46. Que. One of the helpful features for differentiating EDIM virus infection in neonatal mice from that of other enteric infections is ______________.
Ans. The presence of milk in the stomach., p74
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47. Que. Thymic necrosis is one of the pathologic features of EDIM virus infection in neonatal mice that must be differentiated from ______________
Ans. Mouse Thymic Virus (MTV)., p74
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48. Que. EDIM virus infection is best controlled by ______________
Ans. Microbarrier cages and good sanitation., p74
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49. Que. Mouse Hepatitis Virus is a large, pleomorphic, enveloped virus belonging to the family of ______________
Ans. Coronaviridae., p74
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50. Que. Regarding MHV, what factors determine the prevalence and severity of clinical signs?
Ans. Age, strain and immune status of the infected mouse, and strain and tropism of virus., p.75.
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51. Que. What is the most common form of clinical signs in immunocompetent mature mice?
Ans. Usually clinically silent., p.75.
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52. Que. In what age of mice is MHV most likely to cause morbidity, and what are clinical signs seen in affected mice?
Ans. Suckling mice less than 2 weeks old or immunodeficient mice; diarrhea, inappetance, dehydration, weight loss, ruffled pelage, often ending in death. Mild pathogenic strains may cause a chronic wasting in athymic mice (may be accompanied by a progressive paralysis)., p.75.
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53. Que. What species does MHV infect, and how prevalent is it in mouse colonies (what percent of major vivariums have reported it)? How contagious is it, and can it be transmitted from mice to other species ?
Ans. MHV primarily infects mice and is the most common viral infection in mice (60% of major vivariums have reported it). It is highly contagious. There are no reports of transmission from mice to other species., p.75.
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54. Que. How is MHV transmitted? Can vertical, transovarian or transuterine infection occur?
Ans. Via oral or respiratory routes. (With enterotropic strains, feces can also serve as sources of infection). Natural vertical transmission has not been demonstrated. Transovarian and transuterine infections are not specifically addressed. Maternal antibodies do protect against homologous serotypes until weaning., p.75.
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55. Que. What biotypes (enterotropic or polytropic) are suggested to predominate in natural infections of MHV?
Ans. Enterotropic., p.75.
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56. Que. How does enzootic infection with MHV occur, according to what recent evidence suggests?
Ans. Enzootic infection results either from fresh/continuous introduction of immunologically na�ve or deficient mice, OR from recurrent infection of immunocompetent mice with MHV variants that arise from natural mutation., p.75.
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57. Que. Does maternal immunity play a role in MHV infection and, if so, how?
Ans. Maternal immunity protects against homologous strain, but depends on presence of maternal antibodies in the intestine; therefore, susceptibility of young mice increases at weaning., p.75.
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58. Que. Regarding the appearance of infant mice with MHV - picture on p. 75 - do MHV - infected mice continue to nurse? How can you tell whether they are nursing?
Ans. Infant mice can be runted and dehydrated, with an empty stomach (note: as evidenced by lack of "milk spot" in stomach). Compare this with EDIM (p. 73) - mice continue to nurse., p.75.
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59. Que. In MHV infection, _______________ formation is a hallmark of infection in many tissues.
Ans. Syncytia, p76
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60. Que. __________ strains (of MHV) replicate initially in the nasal mucosa. __________ strains infect primarily the __________ and associated lymphoid tissues.
Ans. Polytropic; enterotropic; intestine, p76
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61. Que. Helicobacter muris is more commonly associated with (mice or rats).
Ans. Rats, p76
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62. Que: What pathological changes occur in the intestinal mucosa of surviving Mouse Hepatitis Virus (MHV) mice?
Ans: Mucosal hyperplasia which eventually recedes, p 77
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63. Que: What type of inclusions bodies are found in MHV infected enterocytes?
- Ans: intracytoplasmic inclusions are found in the enterocytes of MHV infected mice.
- , p 77
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64. Que: Which of the following develop transient syncytia in the intestines without necrotic lesions?
Ans: a. Older mice develop transient syncytia without necrotic lesions., p 77
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65. Que: Which of the following commonly develop chronic proliferative bowel disease of varying severity accompanied by syncytia?
Both athymic and SCID mice, p 77
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66. Que. What is the most reliable diagnostic tool for testing MHV infected mice?
Ans: Serological testing, p 77
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67. Que. Is MHV usually symptomatic or asymptomatic?
Ans: asymptomatic, p 77
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68. Que. Which of the following is not diagnostic for detection of MHV?
Ans: Inclusion bodies in the cytoplasm of enterocytes are not diagnostic for MHV in mice, p 77
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69. Que. Which of the following is diagnostic for detecting MHV?
Ans: The use of immunodeficient mice as sentinels, neutralization tests, and detection of synctia augmented by immunohistochemistry are all diagnostic for MHV in mice., p 77
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70.Que. Which serological test is used to differentiate individual MHV strains?
Ans: Neutralization tests., p 77
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71.Que. Differentials for MHV include ___________,___________, ___________, __________ and salmonellosis.
Ans. EDIM, mousepox, reovirus 3 infection, Tyzzer's disease and salmonellosis , p78
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72.Que. Neurological signs for demyelinating lesions must be differentiated from _____________ or noninfectious CNS lesions such as neoplasms, including polyoma-induced tumors in athymic mice.
Ans.Mouse encephalomyeletis, p78
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73. Que. What type of virus is Mouse Encephalomyelitis Virus (MEV)?
Ans. Small, nonenveloped, RNA-containing cardiovirus, p79
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74. Que. How are MEV clinical signs expressed?
Ans. Neurological disease, p79
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75. Que. What is the characteristic sign of MEV?
Ans. Flaccid posterior paralysis possible weakness in fore limbs, mice otherwise alert, p79
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76. Que. How is MEV infection acquired?
Ans. Ingestion, p79
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77. Que. Where does MEV replicate?
Ans. Intestinal mucosa, p79
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78. Que. Neurologic infection with MEV can persist in the brain and spinal cord for how long?
Ans. At least 1 year, p79
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79. Que. Mice with mouse hepatitis virus can be expected to develop immunity and eliminate virus in how many days?
Ans. Within 30 days, p79
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80. Que. How can you eliminate infection of MHV?
Ans. Quarantine with temporary cessation of breeding, p79
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81. Que. Immunity to one strain of mouse encephalomyelitis virus provides _____to other strains.
Ans. Cross-protection, p 80
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82. Que. With regard to mouse encephalomyelitis virus, what _____variants of mouse hepatitis virus may, on occasion, cause similar neurological signs?
Ans. Neurotropic, p 80
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83. Que. _______ or cesarean or embryo derivation can be used to successfully to eliminate mouse encephalomyelitis virus.
Ans. Foster-nursing infant mice, p 80.
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84. Que. Name the disease syndrome caused by Mycoplasma pulmonis.
Ans. Murine Respiratory Mycoplasmosis (MRM) p. 81
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85. Que. ______ and ______ are the most prominent signs of MRM.
Ans. Chattering and dyspnea, p. 81
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86. Que. Experimental inoculation of _____ mice with M. pulmonis has caused systemic infection accompanied by severe arthritis.
Ans. SCID, p. 81
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87. Que. Mycoplasma pulmonis infection is contracted by ______ and can occur in suckling and adult mice.
Ans. Inhalation, p. 81
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88. Que. In utero M. pulmonis infection has been demonstrated in _____ but not mice.
Ans. Rats, p. 81
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89. Que. _____ are significant reservoirs of M. pulmonis infection for mice.
Ans. Rats, p. 81
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90. Que. M. pulmonis infection can have detrimental effects on ciliated epithelium which disrupts _______ ________, exacerbating pulmonary disease.
Ans. Mucociliary transport, p. 81
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91. Que. Intravenous inoculation of M. pulmonis can cause _______ in mice, but it is not a significant feature of natural infection.
Ans. Arthritis, p. 81
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92. Que. _______ background appear to be resistant to pathogenic infection of M. pulmonis, whereas BALB/c, C3H, DBA/2, SWR, AKR, CBA, SJL, and others have varying degrees of increased susceptibility.
Ans. C57BL, p. 81
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93. Que. The initial lesion of MRM is _____ ______.
Ans. Suppurative rhinitis, p. 81
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94. Que. In MRM early inflammatory lesions, if not quickly resolved, progress to prominent _______ ________.
Ans. Squamous metaplasia, p. 81
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95. Que. In MRM pulmonary lesions are typified by __________.
Ans. Bronchopneumonia, p. 81
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96. Que. The _____ _______ ______ should be cultured if MRM is suspected because it is a common site for natural infection.
Ans. Upper respiratory tract, p. 81
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97. Que. Speciation of Mycoplasma can be accomplished by ________ or immunoperoxidase or by growth inhibition.
Ans. Immunofluorescence, p. 81
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98. Que. MRM must be differentiated from bronchopneumonia associated with___________________.
Ans. Cilia � associated respiratory (CAR) bacillus, p82
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99. Que. Athymic and neonatally thymectomized mice are_____________ susceptible than imunocompetent mice to M. pulmonis pneumonia.
Ans. not more, p82
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100. Que. Perhaps one of the most important research complications of Mycoplasma infection is _____________.
Ans. Contamination of cell lines and transplantable tumors., p82
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101. Que. ________ stains may reveal CAR bacilli adherent to the respiratory epithelium.
Ans. Silver, p 82
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102. Que. MRM, CAR and Sendai cause respiratory infection, other causes of respiratory infection in mice include _______________.
Ans. Pneumonia virus of mice, corynebacteriosis, and, in immunodeficient mice, Pneumocystis carinii infection. Combined infections with known pathogens or secondary opportunists also must be considered,, p82
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103. Que. ______________ can eliminate MRM infection but embryos, fetal membranes, and offspring must be tested to rule out contamination.
Ans. Cesarean or embryo rederivation, p82
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104. Que. Treatment with ___________ suppresses clinical disease but does not eliminate infection.
Ans. tetracyclines, p82
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105.Que. Other murine mycoplasmas __________ is antigenically related to Mycoplasma pulmonis.
Ans.Mycoplasma arthritidis, p82
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106.Que. Where has Mycoplasma collis been isolated from and what disease does it cause?
Ans. Mouse genital tract and does not appear to cause natural disease., p83
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107.Que. What is the etiologic agent of rolling disease?
Ans. Mycoplasma neurolyticum., p83
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108. Que. What is the characteristic clinical signs of rolling disease?
Ans. Spasmotic hypertension of the head and the raising of one foreleg followed by intermittent rolling on the long axis of the body. Rolling becomes more constant, but mice occasionally leap or move rapidly. After 1-2 hrs of rolling, animals become comatose and usually die within 4 hrs., p83
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109. Que. Besides Mycoplasma neurolyticum, what is another differential for rolling in mice?
Ans. Pseudomononas-caused otitis, p83
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110. Que. What is the morphologic description of CAR bacillus?
Ans. Cilia-Associated Respiratory (CAR) bacillus is a slender, gram-negative bacillus., p83
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111. Que. What techniques can be use to detect CAR bacillus?
Ans. ELISA for serologic testing, PCR-based diagnostics, histologic assessment with Warthin-Starry or similar stains to visualize argyrophilic bacilli adherent to the apical membranes of bronchial respiratory epithelium, and immunoperoxidase staining., p83
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112. Que. What organism causes Tyzzer�s Disease in mice?
Ans. Clostridium piliforme (formerly Bacillus piliformis), p83
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113. Que. What is the morphologic description of Clostridium piliforme?
Ans. Long, thin, gram-negative spore-forming bacterium., p83
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114.Que. What specific requirement does Clostrium piliforme require for in vitro growth?
Ans. Living cells., p83
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