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Virus

Struktur Umum
 Ukuran
 Kebanyakan
berukuran <0.2
μm
 Mikroskop
elektron
 Virion
 Bisa
menimbulkan
infeksi
Struktur Umum
 Capsid
 Dimiliki semua virus
 Terbuat dari subunit
identik yang disebut
capsomer
 Terbuat dari protein
 nucleoscapsid
 Capsid + asam nukleat
Struktur Umum
 Tiga jenis struktur utama:
 Heliks
 Heliks kontiniu capsomer

yang membentuk
nucleocapsid silindris
 Ikosahedral
 20-sisi dan12 sudut

 Bervariasi dalam
jumlah capsomer
 Sebagian memiliki
selubung

 Kompleks
Ikosahedral

Heliks
Struktur Umum
 Envelope virus
 Kebanyakan animal viruses
 Diperoleh ketika virus meninggalkan sel
inang
 Melindung asam nukleat jik virus berada
di luar sel inang
 Spikes
 Juluran protein keluar envelope
 Penting ketika virus menempel pada sel
inang
 Naked
 Hanya terdiri atas nucleocapsid
 Enveloped
 Diselubungi oleh envelope
Struktur Umum
 Virus kompleks: virus
atipik
 Poxviruses
 Tidak memiliki capsid
tertentu
 Ditutupi oleh lapisan
padat lipoprotein
 Bacteriophage
 Virus menginfeksi dan
bereplikasi dalam sel
bakteri
Target Virus
 Virus memiliki inang dan jaringan target
yang spesifik
 Organisme/jaringan tertentu saja yang bisa
diinfeksi
 Tergantung kepada struktur capsid
 Beberapa virus hanya menginfeksi sel atau
jaringan tertentu dalam inang (tissue tropism)
Asam Nukleat
 Genome Virus
 DNA atau RNA tidak pernah keduanya
 Membawa gen yang dibutuhkan untuk
menginvasi sel inang
 Kemudian mengarahkan aktivitas sel untuk
membuat virus baru
 Jumlah gen virus
 Beberapa sampai ratusan
Asam Nukleat
 Virus DNA
 Biasanya double
stranded (ds)
 Tetapi bisa single
stranded (ss)
 Sirkuler atau linier
Virus DNA
 Virus DNA penyebab penyakit pada manusia: Virus DNA
berenvelop; Virus DNA tidak berenvelope; Virus ssDNA tidak berenvelope
Asam Nukleat
 Virus RNA
 Biasanya ss
 Tetapi ada juga yang ds
 positive-sense RNA
 Genom ssRNA siap untuk segera ditranslasi
 negative-sense RNA
 Genom ssRNA yang harus dikonversi menjadi
bentuk yang tepat sebelum ditranslasi
Virus RNA
 Dikelompokkan berdasarkan envelope, capsid, dan
sifat genom RNA
Virus…. (perbandingan)
 Kebanyakan virus DNA viruses ‘bertunas’ dari
inti sel
 Kebanyakan virus RNA memperbanyak diri
dalam, dan dilepaskan dari sitoplasma
 Kebanyakan virus DNA dan sebagian virus
RNA bisa menjadi penghuni permanen di
dalam sel inang
 Beberapa virus dapat menyeberangi plasenta
dan mengakibatkan gangguan perkembangan
Klasifikasi dan Penamaan Virus
 3 Ordo
 Nama ordo berakhiran –virales
 Herpesvirales

 63 Famili
 Nama famili berakhiran -viridae
 Herpesviridae

 263 genus
 Nama genus berakhiran –virus
 Simplexvirus, Herpes simplex virus I (HSV-I)
Penamaan Virus
 Famili – Herpesviridae
 Genus – Varicellovirus
 Nama umum – chickenpox virus
 Penyakit yang didimbulkan - chickenpox
Cara Virus
Memperbanyak Diri
Siklus Perbanyakan Bakteriofage
 Bakteriofage – virus
bakteri (fage)
 Contoh paling populer
adalah virus yang
menyerang Escherichia coli
 Perbanyakan berlangsung
dengan cara yang sama
seperti virus hewan
 Hanya asam nukleat yang
masuk ke sitoplasma
 Ada dua jenis fage:
 Virulen
 Temperate
 Replikasi virus hewan mirip dengan replikasi
fage
 Virushewan melekat pada membran plasma sel
inang melalui spikes pada capsid atau envelope
Replikasi Genom
 Virus DNA
 Virus RNA
 ds : dua pasang asam nukleat
komplementer
 ss : asam nukleat tidak berpasangan
 Virus pentranskripsi terbalik
1. Virus DNA
 Menggunakan sel inang
menjadi mesin pensintesis
 ds DNA melepaskan DNA :
 Masuk ke inti, lalu ditranskripsi
 mRNA virus ditranslasi dan
protein masuk ke inti
 DNA virus direplikasi di inti
 DNA virus dan protein dirakit
 DNA dapat disisipkan ke DNA
inang
2. Virus RNA
 Informasi genetik dikodekan dalam RNA
 Menggunakan enzim sendiri untuk
mengkopi genomnya
3. Virus Transkripsi Terbalik
 Mensintesis DNA dari genom
ssRNA genome (template)
 Reverse transcriptase
 Terdapat pada virus
 Mensintesis ssDNA dari
ssRNA template
 Mengarahkan pembentukan
untai komplementer dari
template:
 dsDNA virus strand
 Masuk ke inti
 Mengintegrasikan diri ke
genom inang
 Membuat lebih banyak
ssRNA
Sebagian Virus Hewan Dapat Berada Sebagai
Provirus
 Sebagaian virus
DNA dan retrovirus
menyisipkan
genomnya ke
kromosom inang
sebagai provirus
 Retrovirus
menggunakan
reverse transcriptase
untuk mentranskripsi
RNA menjadi DNA
 DNA kemudian
disisipkan ke
kromosom inang
6 Tahap
Replikasi
Virus
1. Absorpsi
2. Penetrasi
3. Replikasi
4. Perakitan
5. Pematangan
6. Pelepasan
1. Absorpsi
 Virus bertemu dengan sel target (sel lemah)
 Absorpsi
secara khusus pada reseptor pada
membran sel
 Melekat pada sel
 Host range:
 Spektrum sel yang dapat diinfeksi virus
 Hepatitis B – sel hati manusia
 Poliovirus – sel saraf dan pencernaan primata

 Rabies – berbagai sel pada banyak mamalia


2. Penetrasi / Uncoating
 Membran dipenetrasi oleh virus atau asam
nukleatnya melalui mekanisme:
 Endositosis
 Virus utuh ditelah dan diselubungi dalam bentuk vakoula atau
vesikula
 Fusi
 Envelope virus bergabung langsung dengan membran
 Terbentuk nukleokapsid, masuk ke sitoplasma
3. Replikasi
 Berbeda-beda, tergantung kepada jenis
virus, virus DNA atau RNA
 Virus DNA umumnya mereplikasi dan
merakit diri dalam nukleus
 Virus RNA biasanya mereplikasi dan
merakit diri dalam sitoplasma
4. & 5. Perakitan dan Pematangan

 Virus matang terbuat dari berbagai


komponen
 Capsid dibuat terlebih dahulu
 Diberi envelop
 Diikuti penyisipan spike
6. Pelepasan
 Virus yang telah dirakit meninggalkan sel inang dengan
dua cara:
 Pertunasan (Budding)
 Eksositosis

 Nukleokapsid berikatan dengan membran dan selanjutnya

melepaskan virus secara bertahap


 Kerusakan sel tidak sekaligus

 Lisis (Lysis)
 Virus kompleks dan nonenveloped dilepaskan ketika sel mati

dan pecah
Kerusakan Sel Inang (Host)
Efek sitopatik:
1. Perubahan dalam ukuran dan bentuk
2. Badan inklusi sitoplasma
3. Badan inklusi nukleus
4. Fusi sel-sel sehingga terbentuk sel berinti
banyak (multinucleated cell).
5. Lisis sel
6. Perubahan DNA
7. Transformasi sel menjadi sel kanker
Transformasi Sel
 Transformasi sel oleh Virus
 Beberapa virus hewan memasuki sel inang, lalu:
 Mengubah materi genetik sel inang secara permanen
 Mengakibatkan kanker
 Sel-sel yang telah ditransformasi:
 Laju pertumbuhan meningkat
 Perubahan dalam kromosom
 Kemampuan membelah tak terbatas pada periode tertentu
 Mengakibatkan tumor

 Oncovirus
 Virus mamalia bisa menginisiasi tumor:
 Papillomavirus – kanker serviks
 Epstein-Barr virus – limfoma Burkitt
Virus DNA Patogenik
Poxvirus  Membuat kulit melepuh, disebut pocks
atau pox
 Virus hewan yang paling besar dan
kompleks
 Genom sangat besar
 dsDNA
Smallpox

 Penyakit virus pertama yang berhasil dieleminasi


melalui vaksinasi
 Eksposure: inhalasi atau kontak kulit
 Infeksi berkaitan dengan demam, malaise,
prostration.
 Vaksinasi rutin diakhiri tahun 1972; kembali tahun 2002
Classic Centrifugal Rash of Smallpox Involving Face and Extremities,
Including the Soles. Photo: National Archives
Classic Centrifugal Rash of Smallpox Involving Face and
Extremities. Photo: National Archives
Classic Smallpox
Rash, Demonstrating
Same Development
Stage (Pustular) of All
Lesions in a Region

Photo: National Archives


Discrete Type of Classical Smallpox Rash
Photo: National Archives
Confluent Type of Classical Smallpox
Rash Photo: National Archives
Herpesvirus
 Semua herpesvirus memiliki latensi
 Lebih parah pada usia lanujut, komoterapi kanker, dan kondisi lain
yang berkaitan dengan sistem imun
 Envelop besar bentuk ikosahedral, dsDNA
Herpesviridae
 Famili besar; 8 diantaranya menginfeksi humans
 HSV-1
 HSV-2
 VZV
 EBV
 CMV
 HHV-6
 HHV-7
 HHV-8
Herpes simplex, tipe 1 (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
Herpes simplex, tipe 2 (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
Herpes pada 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
Varicella-Zoster Virus (VZV)
 HHV-3
 chickenpox &
shingles
 transmitted by
respiratory
droplets & contact
 primary infection
 Chickenpox
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?!
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)
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
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
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
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
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
Diseases of the Skin Caused by Herpesviruses
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
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
Hepadnaviruses
 enveloped DNA
viruses
 never grown in tissue
culture
 unusual genome
containing both
double & single
stranded DNA
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
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
Pathogenesis of Hepatitis B Virus
 Enters through break in skin or mucous membrane
or by injection into bloodstream
 Reaches liver cells
 multipliesand 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
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
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
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
Diseases of the
Enteroviruses
 Coxsackie A viruses
 Infection occurs via
the fecal-oral route
 Produce lesion and
fever
 Herpangina
 Hand-foot-and-mouth
disease
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
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
Hepatitis C Virus
 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
Caliciviruses
 “Cruise ship virus”
 Norwalk agent best known
 believedto 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
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
Rubella
Two clinical forms:
 Postnatal rubella
 generally mild
 malaise, fever, sore throat, lymphadenopathy, rash
 lasting about 3 days

 Congenital rubella
 infectionduring 1st trimester most likely to induce
miscarriage or multiple defects
 Diagnosis based on serological testing
 No specific treatment available
 Attenuated viral vaccine MMR
Coronavirus

 common in domesticated animals


 3 types of human coronaviruses have been
characterized:
 HCV
 causes a cold
 anenteric virus
 Severe Acute Respiratory Syndrome (SARS)
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
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
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
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
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.
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
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
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
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
Parainfluenza
 widespread as influenza
 more benign
 respiratory transmission
 seen mostly in children
 minor cold, bronchitis, bronchopneumonia,
croup
 no specific treatment available
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
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
Rabies
 Rhabdovirus family
 bullet-shaped virions
 enveloped
 slow, progressive zoonotic disease
 Highest mortality rate of any human
disease
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
Rabies
 often diagnosed at
autopsy
 intracellular inclusions
(Negri bodies) in nervous
tissue
 treatment
 passive & active
postexposure immunization
 Days 1, 3, 7, 14, 28, 60
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
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
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
Influenza
 Type B
 strikesevery year
 less common than type A

 Type C
 causes a mild respiratory
illness
 not epidemic
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
Arboviruses

 viruses that spread


by arthropod
vectors
 mosquitoes, ticks,
flies, & gnats
 400 viruses
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
Hemorrhagic Fevers
 Yellow fever
 eliminatedin 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
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
Unconventional
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
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
New Variant Creutzfeldt-Jakob Disease
(vCJD)

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