Viruses and Viral Diseases

1. Viruses and Viral Diseases

2. General Structure of Viruses Size range most <0.2 µm requires electron microscope Virion fully formed virus able to establish an infection

4. General Structure of Viruses Capsids All viruses possess Constructed from identical subunits called capsomers made of protein nucleoscapsid Capsid + nucleic acid

5. General Structure of Viruses Three main structural types: helical Continuous helix of capsomers forming a cylindrical nucleocapsid icosahedral 20-sided with 12 corners vary in the number of capsomers Some are enveloped Complex

7. General Structure of Viruses Viral envelope mostly animal viruses acquired when virus leaves host cell Protects the nucleic acid when the virion is outside the host cell spikes exposed proteins on the outside of the envelope essential for attachment of the virus to the host cell Naked composed only of a nucleocapsid Enveloped surrounded by an envelope

8. General Structure of Viruses Complex viruses: atypical viruses Poxviruses lack typical capsid covered by dense layer of lipoproteins Bacteriophages Virus that infects and replicates within bacterial cells

9. Viral targets Viruses have host range and tissue specificity Host range refers to what organisms the virus can infect depends on capsid structure Many viruses infect certain cell or tissue types within the host (tissue tropism)

10. Nucleic acids Viral genome either DNA or RNA but never both Carries genes necessary to invade host cell then redirect cell’s activity to make new viruses Number of genes varies for each type of virus few to hundreds

11. Nucleic Acids DNA viruses usually double stranded (ds) may be single stranded (ss) circular or linear

12. DNA Viruses DNA viruses causing human disease: enveloped DNA viruses nonenveloped DNA viruses nonenveloped ssDNA viruses

13. Nucleic Acids RNA viruses usually single stranded may be double stranded Segmented versus nonsegmented positive-sense RNA ssRNA genomes ready for immediate translation negative-sense RNA ssRNA genomes that must be converted into proper form

14. RNA Viruses Assigned families based on envelope, capsid, and nature of RNA genome

15. Viruses….a comparison Most DNA viruses are budded off the nucleus Most RNA viruses multiply in & released from the cytoplasm Most DNA & a few RNA viruses can become permanent resident of the host cell Several viruses can cross the placenta & cause developmental disturbances

16. What about Viral classification?? Acellular Completely different way of classifying Will discuss in viral section….

17. Naming Viruses 3 Orders Order name end in –virales Herpesvirales 63 Families Family name ends in -viridae Herpesviridae 263 genera Genus name ends in –virus Simplexvirus, Herpes simplex virus I (HSV-I)

18. Family – Herpesviridae Genus – Varicellovirus Common name – chickenpox virus Disease - chickenpox Naming Viruses

19. Modes of Viral Multiplication

20. Multiplication Cycle in Bacteriophages Bacteriophages – bacterial viruses (phages) Most widely studied are those that infect Escherichia coli Multiplication goes through similar stages as animal viruses Only the nucleic acid enters the cytoplasm uncoating not necessary Two types of phages: Virulent Temperate

21. Animal virus replication has similarities to phage replication Animal viruses attach to host plasma membrane via spikes on the capsid or envelope

22. Genome Replication DNA viruses RNA viruses ds Two complementary paired nucleic acids ss Unpaired nucleic acids Reverse transcribing viruses

23. 1. DNA Viruses Use host cell’s synthesizing machinery ds DNA releases its DNA then: Enters nucleus Is transcribed Viral mRNA translated and proteins enter nucleus Viral DNA replicated in nucleus Viral DNA and proteins assembled CAN insert itself into host DNA

24. 2. RNA Viruses Genetic information encoded in RNA Use own enzymes to copy their genomes Can be: (-) genome and must be converted before translation (-) that can be converted to DNA or dsRNA (+) genome ready to be translated into proteins

25. (+) genome ready to be translated into proteins Penetration and uncoating of viral RNA Directly translated on host cell ribosomes into viral proteins (-) genome synthesized to produce for final assembly (-) template used to make (+) replicates RNA strands assembled

26. 3. Reverse Transcribing Viruses Synthesize DNA using their ssRNA genome as a template Reverse transcriptase Packaged with each viral particle Synthesizes ssDNA from their template Directs formation of complementary strand of above =dsDNA virus strand Enters nucleus integrated into host genome We then make more ssRNA

27. Some Animal Viruses Can Exist as Proviruses Some DNA viruses and retroviruses insert their genome into the host chromosome as a provirus Retroviruses use reverse transcriptase to transcribe their RNA to DNA It can then be inserted into the host chromosome

28. 6 Steps in Viral Replication adsorption penetration replication assembly maturation release

29. 1. Adsorption and Host Range Virus coincidentally collides with a susceptible host cell adsorbs specifically to receptor sites on the cell membrane Attachment host range Spectrum of cells a virus can infect hepatitis B – human liver cells poliovirus – primate intestinal and nerve cells Rabies – various cells of many mammals

30. 2. Penetration/Uncoating Flexible cell membrane penetrated by the whole virus (or its nucleic acid) by: endocytosis entire virus engulfed and enclosed in a vacuole or vesicle fusion envelope merges directly with membrane Results in nucleocapsid’s entry into cytoplasm

31. 3. Replication Varies depending on whether the virus is a DNA or RNA virus DNA viruses generally are replicated and assembled in the nucleus RNA viruses generally are replicated and assembled in the cytoplasm

32. 4. & 5. Assembly and Maturation Mature viruses made from various parts Capsid laid down first Enveloped Insert viral spikes

33. 6. Release Assembled viruses leave host cell in one of two ways: budding exocytosis nucleocapsid binds to membrane which pinches off and sheds the viruses gradually cell is not immediately destroyed lysis nonenveloped and complex viruses released when cell dies and ruptures

34. Damage to Host Cell Cytopathic effects - virus-induced damage to cells Changes in size & shape Cytoplasmic inclusion bodies Nuclear inclusion bodies Cells fuse to form multinucleated cells Cell lysis Alter DNA Transform cells into cancerous cells

36. Transformation transformation of the cell Some animal viruses enter host cell Permanently alter its genetic material resulting in cancer Transformed cells have: increased rate of growth alterations in chromosomes capacity to divide for indefinite time periods resulting in tumors oncoviruses Mammalian viruses capable of initiating tumors Papillomavirus – cervical cancer Epstein-Barr virus – Burkitt’s lymphoma

37. Techniques in Cultivating and Identifying Animal Viruses Obligate intracellular parasites require appropriate cells to replicate In vitro In vivo Methods used: cell (tissue) cultures bird embryos live animal inoculation

38. Techniques in Cultivating and Identifying Animal Viruses Cell (tissue) cultures cultured cells grow in sheets that support viral replication permit observation for cytopathic effect

39. Techniques in Cultivating and Identifying Animal Viruses Bird embryos incubating egg is an ideal system virus is injected through the shell

40. Techniques in Cultivating and Identifying Animal Viruses live animal inoculation occasionally used when necessary

41. Pathogenic DNA Viruses

42. Poxviruses Produce eruptive skin pustules called pocks or pox Largest and most complex animal viruses largest genome of all viruses dsDNA variola – cause of smallpox vaccinia – closely related virus used in vaccines monkeypox cowpox

44. Smallpox first disease to be eliminated by vaccination exposure through inhalation or skin contact infection associated with fever, malaise, prostration, & a rash Variola major highly virulent, caused toxemia, shock, & intravascular coagulation Variola minor less virulent routine vaccination ended in US in 1972 reintroduced in 2002

45. Molluscum Contagiosum caused by unclassified poxvirus primarily an infection of children transmitted by direct contact and fomites AIDS patients suffer atypical form attacks the skin of the face forms tumorlike growths Treatment freezing, electric cautery, chemical agents

46. The Herpesviruses All members show latency and cause recurrent infection more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses Large enveloped icosahedral dsDNA

47. Herpesviridae large Family; 8 infect humans HSV-1 HSV-2 VZV EBV CMV HHV-6 HHV-7 HHV-8

48. Epidemiology of Herpes Simplex Viruses:HSV-1 & 2 Transmission direct exposure to secretions containing the virus active lesions most significant source genital herpes can be transmitted in the absence of lesions HSV multiplies in sensory neurons, moves to ganglia HSV-1 enters 5th cranial nerve HSV-2 enters lumbosacral spinal nerve trunk ganglia

49. Epidemiology of Herpes Simplex Viruses Recurrent infection triggered by various stimuli fever, UV radiation, stress, mechanical injury Newly formed viruses migrate to body surface produce a local skin or membrane lesion

50. Type 1 Herpes Simplex (HSV – 1) Herpes labialis fever blisters, cold sores most common recurrent HSV-1 infection vesicles occur on mucocutaneous junction of lips or adjacent skin itching and tingling prior to vesicle formation lesion crusts over in 2-3 days and heals Herpetic gingivostomatitis infection of oropharynx in young children fever, sore throat, swollen lymph nodes Herpetic keratitis ocular herpes

51. Type 2 Herpes Simplex (HSV – 2) Genital herpes herpes genitalia starts with malaise, anorexia, fever, and bilateral swelling and tenderness in the groin clusters of sensitive vesicles on the genitalia, perineum, and buttocks urethritis, painful urination Recurrent bouts usually less severe triggered by menstruation, stress, and concurrent bacterial infection

52. Herpes of the Newborn HSV-1 and HSV-2 Potentially fatal in the neonate and fetus Infant contaminated by mother before or during birth hand transmission by mother to infant Infection of mouth, skin, eyes, CNS Preventative screening of pregnant women delivery by C-section if outbreak at the time of birth

53. Diagnosis, Treatment, and Control Vesicles and exudate are typical diagnostic symptoms scrapings from base of lesions showing giant cells culture and specific tests for diagnosing severe or disseminated HSV

54. Varicella-Zoster Virus (VZV) HHV-3 chickenpox & shingles transmitted by respiratory droplets & contact primary infection Chickenpox

55. Varicella-Zoster Virus (VZV) virus enters neurons & remains latent later reactivation of the virus results in shingles vesicles localized to distinctive areas dermatomes treatment acyclovir, famciclovir, interferon live attenuated vaccine Always effective?!

56. Epstein-Barr Virus (EBV) HHV-4 infects lymphoid tissue & salivary glands transmission direct oral contact & contamination with saliva by mid-life 90-95% of all people are infected causes mononucleosis sore throat, high fever, cervical lymphadenopathy Complications include: heart defects facial paralysis rupture of the spleen jaundice (hepatitis)

57. Epstein-Barr Virus (EBV) 30-50 day incubation most cases asymptomatic Burkitt’s lymphoma associated with chronic co-infections with malaria nasopharyngeal carcinoma in Chinese & African men

58. Cytomegalovirus (CMV) HHV-5 produce giant cells with nuclear & cytoplasmic inclusions transmitted in saliva, respiratory mucus, milk, urine, semen, cervical secretions & feces commonly latent in various tissues most infections are asymptomatic 3 groups develop a more virulent form of disease fetuses, newborns, immunodeficient adults

59. CMV perinatal CMV infection mostly asymptomatic or a mononucleosis-like syndrome newborns may exhibit enlarged liver & spleen, jaundice, capillary bleeding, microcephaly, & ocular inflammation may be fatal transplant patients pneumonitis, hepatitis, myocarditis, meningoencephalitis Treatment ganciclovir, valvcyclovir

60. Human Herpes Virus 6 HHV-6 T-lymphotropic virus transmitted by close contact very common causes roseola An acute febrile disease in babies 2-12 months can cause encephalitis, cancer

61. Human Herpes Virus 6 begins with fever, followed by a faint maculopapular rash usually self-limited adults may get mono-like symptoms, lymphadenopathy, hepatitis over 70% of MS patients show signs of infection

62. Diseases of the Skin Caused by Herpesviruses

63. Papillomavirus papilloma benign, squamous epithelial growth, wart or verruca caused by 100 different strains of HPV common seed warts Fingers plantar warts soles of feet genital warts prevalent STD transmissible through direct contact or contaminated fomites Incubation 2 weeks – more than a year

64. Genital Warts most common STD in US over 6 M new cases each year 30 M carriers of one of the 5 types of HPV associated with genital warts strong association with cervical & penile cancer Treatment cauterization, freezing, laser surgery, immunotherapy

66. Hepadnaviruses enveloped DNA viruses never grown in tissue culture unusual genome containing both double & single stranded DNA

67. The Viral Agents of Hepatitis Hepatitis inflammatory disease of liver cells may result from several viruses (RNA) Interferes with liver’s excretion of bile pigments bilirubin accumulates in blood and tissues causing jaundice 3 principal viruses involved in hepatitis: hepatitis B hepatitis A hepatitis C

68. Hepatitis B Virus 107 virions/mL blood minute amounts of blood can transmit infection sexually transmitted high incidence among homosexuals & drug addicts can become a chronic infection

69. Pathogenesis of Hepatitis B Virus Enters through break in skin or mucous membrane or by injection into bloodstream Reaches liver cells multiplies and releases viruses into blood average 7 week incubation continuously seeds blood with viruses increases risk of liver cancer May develop liver disease with necrosis and cirrhosis Some experience malaise, fever, chills, anorexia, abdominal discomfort and diarrhea

70. Parvoviruses nonenveloped icosahedral, ssDNA small diameter & genome size B19 cause of fifth disease erythema infectiosum rash of childhood Child may have fever & rash on cheeks Severe fatal anemia can result if pregnant woman transmits virus to fetus

71. Pathogenic RNA Viruses Naked, positive ssRNA Enveloped, positive ssRNA Enveloped, positive ssRNA with Reverse transcriptase Enveloped, unsegmented, negative ssRNA Enveloped, segmented, negative ssRNA Naked, segmente dsRNA

72. Human Rhinovirus (HRV) More than 110 serotypes (strains) associated with the common cold Sensitive to acidic environments optimum temperature is 33oC Unique molecular surface makes development of a vaccine unlikely Endemic with many strains circulating in the population at one time acquired from contaminated hands and fomites

73. Diseases of the Enteroviruses Coxsackie A viruses Infection occurs via the fecal-oral route Produce lesion and fever Herpangina Hand-foot-and-mouth disease

74. Poliovirus and Poliomyelitis naked capsid can survive stomach acids when ingested Poliomyelitis (polio) acute enteroviral infection of the spinal cord can cause neuromuscular paralysis Worldwide vaccination programs have reduced the number of cases eradication is expected

75. Hepatitis A Virus and Infectious Hepatitis Not carried chronically principal reservoirs are asymptomatic, short-term carriers or people with clinical disease Fecal-oral transmission Most infections subclinical or vague, flu-like symptoms occur No specific treatment once the symptoms begin Inactivated viral vaccine Pooled immune serum globulin for those entering into endemic areas

76. Hepatitis C virus (HCV) belongs to the Flaviviridae family transmitted by blood Few symptoms are associated with primary infection Most cases develop a symptomless chronic infection, involving cirrhosis and other complications HCV damage is the primary reason for liver transplants in the United States Damage is accelerated by alcoholism and drug use Hepatitis C Virus

77. Caliciviruses “Cruise ship virus” Norwalk agent best known believed to cause 1/3rd of all viral gastroenteritis cases Transmitted by fecal-oral route Infection in all ages at any time of year Acute onset, nausea, vomiting, cramps, diarrhea, chills Rapid and complete recovery

78. Rubella Caused by Rubivirus, a Togavirus ssRNA with a loose envelope German measles Most cases reported are adolescents and young adults Transmitted through contact with respiratory secretions

79. Rubella Two clinical forms: Postnatal rubella generally mild malaise, fever, sore throat, lymphadenopathy, rash lasting about 3 days Congenital rubella infection during 1st trimester most likely to induce miscarriage or multiple defects Diagnosis based on serological testing No specific treatment available Attenuated viral vaccine MMR

80. Coronavirus common in domesticated animals 3 types of human coronaviruses have been characterized: HCV causes a cold an enteric virus Severe Acute Respiratory Syndrome (SARS)

81. SARS Severe Acute Respiratory Syndrome-Associated Coronavirus Newly emerging disease – 2002 Transmitted through droplet or direct contact Fever, body aches, and malaise severe cases can result in respiratory distress and death Diagnosis relies on exclusion of other likely agents 10% cases fatal Treatment is supportive

82. Retroviruses enveloped, ssRNA viruses encode reverse transcriptase enzyme which makes a DNA copy of their RNA genome Human Immunodeficiency Virus (HIV) cause of Acquired Immunodeficiency Syndrome (AIDS) HIV-1 & HIV-2

83. Retroviruses HIV normally infects the immune system cells, including T lymphocytes (CD4+ T cells) Incapacitation of T lymphocytes allows opportunistic pathogens to infect the body HIV also infects and paralyzes B lymphocytes

84. Epidemiology of HIV Infections Transmission occurs by direct and specific routes mainly through sexual intercourse and transfer of blood or blood products babies can be infected before or during birth, and from breast feeding HIV does not survive long outside of the body

85. Facts…. First recognized in 1981 “Patient 0” 6th most common cause of death among people aged 25-44 years in the U.S. Men account for 70% of new infections IV drug abusers can be HIV carriers significant factor in spread to heterosexual population In 2006, the number of infected individuals worldwide is estimated to be 45 million ~1 million in the U.S.

86. Risk Categories homosexual or bisexual males – 45% intravenous drug users – 30% heterosexual partners of HIV carriers – 11% blood transfusions & blood products – since testing, no longer a serious risk inapparent or unknown risk – 9% - (due to denial, death, unavailability) congenital or neonatal – can be reduced with antiviral drugs

87. Pathogenesis and Virulence Factors of HIV Enters through mucous membrane or skin travels to dendritic phagocytes beneath the epithelium multiplies and is shed Virus taken up and amplified by macrophages in the skin, lymph organs, bone marrow, and blood HIV attaches to CD4 and coreceptor HIV fuses with cell membrane Reverse transcriptase makes a DNA copy of RNA Viral DNA is integrated into host chromosome (provirus) Can produce a lytic infection or remain latent

89. Effects of HIV infection Primary effects extreme leukopenia lymphocytes in particular formation of giant T cells and other syncytia allows the virus to spread directly from cell to cell Infected macrophages release the virus in central nervous system toxic effect, inflammation Secondary effects Destruction on CD4 lymphocytes allows for opportunistic infections and malignancies

90. Signs and Symptoms of HIV Infections and AIDS Initial infection mononucleosis-like symptoms that soon disappear Asymptomatic phase 2-15 years (avg. 10) Antibodies are detectable 8-16 weeks after infection When T4 cell levels fall below 200/mL AIDS symptoms appear

91. Diagnosis of HIV Infection Testing based on detection of antibodies specific to the virus in serum or other fluids Initial screening ELISA rapid results but may result in false positives Follow up with Western blot analysis to rule out false positives False negatives can also occur persons who may have been exposed should be tested a second time 3-6 months later

92. Diagnosis of AIDS Made when a person meets the criteria: Positive for the virus, and They fulfill one of the additional criteria: They have a CD4 count of fewer than 200 cells/ml of blood Their CD4 cells account for fewer than 14% of all lymphocytes They experience one or more of a CDC-provided list of AIDS-defining illnesses

93. Azidotheymidine (AZT) first drug used for treatment interferes with reverse transcriptase activity HIV can become resistant to some antivirals requires a cocktail of drugs called highly active antiretroviral therapy (HAART) HAART reduces the risk of HIV transmission and can extend life of patients by about 8 years A vaccine has not yet been developed HIV continually mutates and recombines makes vaccine development difficult HIV Treatment

94. Paramyxoviruses enveloped ssRNA Paramyxoviruses (parainfluenza, mumps virus) Morbillivirus (measles virus) Pnuemonovirus (respiratory syncytia virus) respiratory transmission virus causes infected cells to fuse with neighboring cells syncytium or multinucleated giant cells form

95. Measles Morbillivirus “red measles” & “rubeola” very contagious transmitted by respiratory aerosols humans the only reservoir sore throat, dry cough, headache, conjunctivitis, lymphadenitis, fever, Koplik spots oral lesions Rash

96. Measles most serious complication is subacute sclerosing panencephalitis (SSPE) progressive neurological degeneration of the cerebral cortex, white matter & brain stem 1 case in a million infections involves a defective virus spreading through the brain by cell fusion & destroys cells leads to coma & death in months or years attenuated viral vaccine MMR

97. Parainfluenza widespread as influenza more benign respiratory transmission seen mostly in children minor cold, bronchitis, bronchopneumonia, croup no specific treatment available

98. Mumps epidemic parotitis self-limited, associated with painful swelling of parotid salivary glands humans are the only reservoir incubation 2-3 weeks fever, muscle pain & malaise, classic swelling of both cheeks in 20-30% of infected males, epididymis & testes become infected sterilization is rare live attenuated vaccine MMR

99. RSV also called Pneumonvirus infects upper respiratory tract produces giant multinucleate cells most prevalent cause of respiratory infection in children 6 months or younger epithelia of nose & eye portal of entry rhinitis, wheezing, otitis, croup

100. Rabies Rhabdovirus family bullet-shaped virions enveloped slow, progressive zoonotic disease Highest mortality rate of any human disease

101. Rabies virus enters through bite, grows at trauma site for a week enters nerve endings & advances toward the ganglia, spinal cord & brain dumb form of rabies paralyzed, stuporous furious form of rabies agitation, disorientation, seizures, twitching, hydrophobia

102. Rabies often diagnosed at autopsy intracellular inclusions (Negri bodies) in nervous tissue treatment passive & active postexposure immunization Days 1, 3, 7, 14, 28, 60

103. Influenza ssRNA Belongs to the Orthomyxoviridae family 3 distinct influenza virus types: A, B, C Virus attaches to, and multiplies in, the cells of the respiratory tract finished viruses are assembled and budded off

104. Influenza It contains two types of spikes Hemagglutin (H) helps the virion attach and penetrate host cells Neuraminidase (N) helps release virions from the host cell after replication and assembly

105. Influenza Type A acute, highly contagious respiratory illness causes rapid shedding of cells, stripping the respiratory epithelium, severe inflammation fever, headache, myalgia, pharyngeal pain, shortness of breath, coughing annual trivalent vaccine New flu strain evolves every year requires development of a new vaccine

106. Influenza Type B strikes every year less common than type A Type C causes a mild respiratory illness not epidemic

107. Influenza Complications such as pneumonia or secondary infections occur in: Infants Elderly Immunocompromised people Guillain-Barré syndrome occurs when the body damages its own peripheral nerve cells Reye syndrome often occurs in children who take aspirin to treat pain and fever

108. Arboviruses viruses that spread by arthropod vectors mosquitoes, ticks, flies, & gnats 400 viruses

109. The Influence of the Vector Vectors and viruses tend to be clustered in the tropics and subtropics many temperate zones have periodic epidemics life cycles are closely tied to the ecology of the vectors peak incidence when the arthropod is actively feeding and reproducing Humans can serve as dead-end, accidental hosts or they can be a maintenance reservoir Controlling the vector controls the disease

110. Characteristics of Arbovirus Infections Viral encephalitis brain, meninges, and spinal cord are involved convulsions, tremor, paralysis, loss of coordination, memory deficits, changes in speech and personality, coma survivors may experience permanent brain damage Treatment is supportive

111. N.A.Viruses Colorado tick fever (CTF) most common tick-borne viral fever in U.S. Rocky Mountain states Western equine encephalitis (WEE) western U.S. and Canada extremely dangerous to infants and small children Eastern equine encephalitis (EEE) eastern U.S. and Canada

112. N.A. Viruses California encephalitis; 2 different strains: California strain western states little human impact LaCrosse strain eastern U.S. and Canada prevalent cause of viral encephalitis St. Louis encephalitis (SLE) most common of all in America epidemics in midwestern and southern states inapparent infections are very common

113. N.A. Viruses West Nile encephalitis 1999 2000 2001

114. Hemorrhagic Fevers Yellow fever eliminated in U.S. Two patterns of transmission: urban cycle humans and mosquitoes sylvan cycle forest monkeys and mosquitoes South America Acute fever, headache, muscle pain may progress to oral hemorrhage, nosebleed, vomiting, jaundice, and liver and kidney damage significant mortality rate

115. Hemorrhagic Fevers Dengue fever flavivirus carried by Aedes mosquito not in U.S. usually mild infection dengue hemorrhagic shock syndrome, breakbone fever extreme muscle and joint pain can be fatal

116. Unconventional

117. Unconventional Viruslike Agents cause spongioform encephalopathies transmissable, fatal, chronic infections of the nervous system Creutzfeldt-Jakob Disease (CJD) New variant CJD Kuru caused by prions infectious proteins

119. Prions proteinaceous infectious particles misfolded proteins contain no nucleic acid Result in amyloid plaques Extremely resistant to usual sterilization techniques Cause transmissible spongiform encephalopathies (TSEs) in humans and animals Neurodegenerative diseases with long incubation periods

120. Variant CJD became apparent in the late 1990’s after eating meat from cattle afflicted with bovine spongiform encephalopathy (BSE) Difficult to diagnose requires examination of biopsied brain or nervous tissue Prevention relies on avoidance of contaminated tissue Treatment focuses on easing symptoms Prions