Wsu Exam 4 Viral Cns Infections

Front 1

Protein and virus?

-highly basic, forms ribonucleoprotein complex with genomic RNA

- terminal domain has a signal sequence to translocate the prM protein into the lumen of the ER to be processed as membrane protein

Back 1

C Protein of flaviviruses

Front 2

What herpesviruses infect CNS?

Back 2

HSV encephalitis

Herpes B Virus infections

Varicella-Zoster Virus infections

Congenital CMV infection

Front 3

What does the P1 region of Picornoviruses encode for?

Back 3

viral capsid proteins (VP1, VP2, VP3 and VP4)

Front 4

Virus?

-Nonenveloped icosahedral virions

-Circular, dsDNA genomes

-Genome size is about 5 kb
->containing 6 genes

-Nuclear replicating

-Highly dependent on cellular enzymes for DNA replication and gene expression

Back 4

Polyomaviruses
including:
JC virus - assoc with Progresive mulitifocal Leukoencephalopathy

BK virus

Front 5

Virus?
ssRNA virus positive strand
enveloped, icosahedral nucleocapside

Febrile, influenza-like illness
Moderate to high fever
Headache, sore throat, backache, fatigue
Rash, lymphadenopathy, Myalgias
Acute aseptic meningitis or encephalitis

Reservoir: Birds
Vector mosquito, ticks
Infects:
humans, horses, bats, squirrels and domestic rabbits

Back 5

West Nile Virus

Front 6

What are the major infected cell type in HIV-1 encephalitis?

Back 6

There is good evidence that HIV-1 gains access to the central nervous system through

infected MACROPHAGES

as cells of the monocyte/macrophage lineage in the brain are the major infected cell types in vivo.

Front 7

Virus?

linear, ssRNA, positive sense ranging from 10 to
11 kbp.

The 3’ end is not polyadenylated, and 5’ is capped.

Back 7

Flavivirus

Front 8

What is the post exposure txmt for Rabies virus?

Back 8

1) Local wound treatment: If you are exposed to a potentially rabid animal wash the wound thoroughly with soap and water, and seek medical attention immediately.

2) Passive immunization: human rabies immune globins (HRIG) collected from immunized persons and administer to the people exposed to rabies.

3) Vaccination: Immunize the person with human diploid cell rabies vaccine (HDCV) which has inactivated virus.

Front 9

Virus family?

California Encephalitis

Back 9

Bunyaviruses

Front 10

Virus?

Non-segmented
(-)ssRNA

• Enveloped
• Helical nucleocapsid
• External glycoprotein coat & periph matrix prot.
• Ribonucleoprotein (RNP): MOST infectious component of virus
• Replicated in cytoplasm

• Symptoms: difficulty breathing and swallowing, increased muscle tone, hydrophobia, cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells, neuronal necrosis

Back 10

Rhabdovirus (Rabies)

• “Bullet shaped virus”

Front 11

Virus and disease?

dsDNA virus enveloped & icosahedral

the most common form of sporadic fatal encephalitis in adults

Focal encephalitis with fever, altered consciousness and behavior, disordered thinking

temporal lobe of the brain is most often involved.

Back 11

HSV Encephalitis

HSV-1

Front 12

What is the family and subfamily of the JC virus and BK virus?

Back 12

Family: Papovaviridae, Subfamily: Polyomavirinae

Front 13

What are the potential target which could inhibit HIV replication w/o affecting host fxn?

Back 13

(1) Viral entry into host cell,
(2) Reverse transcriptase,
(3) Integrase
(4) Post-transcriptional regulation
(5) Protease

Front 14

What virues are part of the flavivirus family?

Back 14

West nile virus
Yellow virus
Dengue
St. Louis Encephalitis
Hep C

Front 15

What virus has cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells and Neuronal necrosis?

Back 15

Rabies virus
-Zoonotic disease

Front 16

Virus and disease?

Initial symptoms are usually indicative of focal cerebral involvement:
personality alterations, intellectual deficits, loss of motor skills, sensory loss

Less frequently, initial symptoms may indicate cerebellar or brain stem involvement: e.g., difficulty speaking, swallowing, ataxia

Rapid progression. Death usually occurs within 2 – 12 months.

Back 16

JC virus

PML
Progressive Multifocal Leukoencephalopathy

Front 17

Virus?
ssRNA (+) virus
Naked, icosahedral capsid

•Labile in low pH
•Grows at 33°C
•Infects URT
•Aerosol transmission
•Nasopharyngeal region infections (common cold)

Back 17

Rhinovirus
-part of picornaviruses

Front 18

Virus?

ssRNA (+)
enveloped Icosahedral capsid
-rare and fatal

-> Fever, General muscle pains, Severe headache, Permanent brain damage, Seizures and coma.

-> Replication occurs in vascular endothelium and lymphatic cells of the lymphoreticular system

-> Small hemorrhages in the brain
Extensive neuronal damage

Reservoir: Birds (marsh birds)
Carrier: Mosquitoes
Infects: Humans and horses, birds such as pheasants, quail and ostriches

Back 18

Eastern equine encephalitis
-part of Togaviruses

Front 19

What is the 5’-noncoding region which contains a ‘clover-leaf’ secondary structure for the picornaviruses?

Back 19

Internal Ribosome Entry Site (IRES)

Front 20

Virus? And specific type

ssRNA (+)
naked, icosahedral

flaccid paralysis that results from destruction of motor neurons in the anterior horn of the spinal cord

Back 20

type 1 poliovirus
-part of picornaviruses

Front 21

Virus?

12.5 kb length, no poly-A-tail, lack of 5’ cap. Structural genes are encoded by 5’ end of the RNA

Back 21

Pestivirus
-animal virus
-part of flavivirus family

Front 22

What interaction for host cell entry is unique to the Dengu Virus – 2?

Back 22

DEN-2 (dengue virus-2) interacts with:

1. glycosaminoglycans
2. heparin sulfate

Front 23

What 2 areas of HIV replication have drugs been developed to inhibit replication?

Back 23

reverse transcriptase and protease

Front 24

What RNA-dependent RNA polymerase for
1. Picornovirus
2. Flavivirus

Back 24

1. 3D
2. NS5

Front 25

What RNA-dependent RNA polymerase for Picornovirus?

Back 25

3D

Front 26

What RNA-dependent RNA polymerase for Flavivirus?

Back 26

NS5

Front 27

Virus?

ssRNA (+) enveloped, icosahedral capsid

High fever, chills, headache, vomiting, jaundice, hemorrhagic complications, renal failure

Arbovirus: mosquito Aedes Aegypti

Back 27

Yellow fever
-part of flaviviruses

Front 28

Virus ?

Transmissible by bite or by contact of saliva with mucous membranes

Highly pathogenic for humans, with a high frequency of fatal encephalitis

Back 28

Herpes B Virus
-only member of hepadnavirus family Cercopithecine Herpesvirus 1

NOTE:
-> DO NOT GET THIS CONFUSED WITH HEPETITIS B

Front 29

Protein and virus?

similar hydrophobic sequences at C-terminal of the prM cause the translocation of the E protein into lumen.

- will be cleaved to pr and M
upon maturation of virion

Back 29

PrM protein:
flavivirus

Front 30

Stimulates the 3D pol activity as well as the proteolytic activity of 3CDpro.

Back 30

3AB protein
Viral non-structural proteins
Picornovirus

Front 31

What mediate the cleave process of eIF-4G by picornoviruses?

Back 31

The 2A viral proteinase of enterovirus & rhinovirus and the L protein of aphthovirus is expected to mediate the cleavage process of eIF-4G.

->deletion of part of 2A protien is LETHAL to virus

Front 32

Virus family?
- enveloped virions

- Contains single stranded positive–sense RNA, large proteins are directly synthesized from this transcript. Large proteins cleaved to regulatory and structural proteins.

- Non structural proteins at the 5’ end of genome, structural proteins (capsid andenvelope) at 3’ end *** Very Imp!!

• Replication in cytoplasm as in polio and flaviviruses

Back 32

TOGAVIRUS

Eastern Equine Encephalitis (EEE)
Western Equine Encephalitis (WEE)
Rubella virus

Front 33

Enhances the membrane vasicularization in infected host cells, which are the sites of RNA

->required for RNA synthesis

Back 33

2B protein
Viral non-structural proteins
Picornovirus

Front 34

Where is the primary target for picornovirues and where do they replicate?

Back 34

Primary target is lymphoid tissue of oropharynx & gut -> transient viremia ->CNS infection / replication (in grey matter)

-> replication of picornaviruses takes place exclusively in cytoplasm**

-particularly in motor neurons of the anterior horns of the spinal cord and brain stem

Front 35

Virus?
(+) ssRNA
• Labile in low pH
• Grows at 33°C
• Infects URT
• Aerosol transmission
• Foot & mouth disease (FMD) in cloven footed animals (Foot & mouth disease virus O )

Back 35

Aphthovirus
- Part of Picornavirus family

Front 36

What diseases are associated with each other using Protease fingerprinting?

Back 36

a molecular characterization of the PrP fragment resistant to digestion by proteolytic enzymes

-> shows that NV-CJD prions resemble BSE (KEY)***
Not classical CJD prionds
->strongly suggest transmission from cattle

Front 37

What model of CJD is explained by equilibrium existing btwn PrPc and PrPSc with arrgreated shifting to the role of PrPSc?

Back 37

Seeding Model

Front 38

What enzyme is needed for polyprotien cleavage for picornoviruses?

Back 38

virus encoaded proteases

Front 39

Virus and disease?
Circular dsDNA nonenveloped icosahedral

Pathological changes may occur in cerebrum, cerebellum or brain stem

-> lesions are characterized by the loss of myelin.
♦ In the cerebrum, this typically occurs in the subcortical region (deep white matter).
♦ Cerebral cortex and gray matter appear normal.

Loss of myelination is due to virus replication in oligodendrocytes.

Little or no inflammation.

Back 39

JC virus
-part of polyomaviruses (subfamily)
-part of papovaviridae family of viruses
PML
Progressive Multifocal Leukoencephalopathy

Front 40

How do flavivirusus enter host cells?

Back 40

Flaviviruses gains entry into a host cell through receptor mediated endocytosis.

The envelope protein plays a major role in virion attachment to host cells.

additional mechanism of flavivirus binding, typically known as antibody-dependent enhancement (ADE)

Front 41

proteins which may play an essential role in the pathogenesis of the HTLV-1 associated diseases

Back 41

Structural regulatory (Tax and Rex) and several additional proteins

Front 42

What are the capsid proteins for

1. Picornoviruses
2. Flaviviruses

Back 42

1. VP1, VP2, VP3 and VP4

2. C protein

Front 43

What are the capsid proteins for Picornoviruses?

Back 43

VP1, VP2, VP3 and VP4

Front 44

What are the capsid proteins for Flaviviruses?

Back 44

C protein

Front 45

Disease?

Thought to be caused by transmission of the Bovine Spongiform Encephalopathy (BSE) to humans.

Psychiatric symptoms,
neurological deficits,
cognitive decline

age of onset = 26

Back 45

Variant (vCJD)
CJD is the most common TSE affecting humans

Front 46

+ ssRNA
Retroviridae
Oncornavirinae

Back 46

Human T-cell Leukemia virus

Front 47

What are the CNS complications for Varicella?

Back 47

1. Transcient cerebellar ataxia
2. Aseptic meningitis
3. cerebral encephalitis
4. transverse myelitis

Front 48

How is PML dx?

Back 48

MRI or CT imaging for lesions in subcortical and deep white matter

PCR detection of JCV in CSF

Brain biopsy to verify presence of JCV and to eliminate other infections which may mimic PML: Toxoplasma gondii, Cryptococcus neoformans, Mycobacterium tuberculosis that would be seen in an immunocompromised pt

Front 49

How does the picornoviuses shut down host cell genes?

Back 49

Piconaviruses “shut off” the host cell genes while not affecting synthesis of their own proteins. Shutoff of host cell translation occurs due to cleavage of the cellular protein eIF-4G

(eIF-4G: eukaryotic Initiation Factor 4G), a component of the 220kD “cap-binding complex” (CBC or CBP)

Front 50

What are pathologic changes in the CNS associated with Creutzfeldt - Jakob disease?

Back 50

spongiform degeneration
astrocytosis
cerebral atrophy
neuronal vacuolization
amyloid plaques
lack of inflammation

NOT lymphocytic infiltration

Front 51

Virus?

ssRNA (+) enveloped, icosahedral
fever, headache, pain behind eyes, lumbosacral pain (no significant deaths)

Arbovirus

Back 51

Dengue
-part of flavivirus family

Front 52

a molecular characterization of the PrP
fragment resistant to digestion by proteolytic enzymes

Back 52

Protease fingerprinting

Front 53

Disease?

♦ Impaired cognitive function
♦ Ataxia
♦ Spongiform degeneration
♦ Activated astrocytes and microglial cells

Back 53

Transmissible Spongiform Encephalopathies (TSEs)

Due to prions

Front 54

a protease, implicated between p2 and p3 cleavage

Back 54

3C protein
Viral non-structural proteins
Picornovirus

Front 55

Protein and virus?

translocates the NS1 protein into lumen of ER

-> play a critical role in binding to cell surface receptors and subsequent viral entry

Back 55

E protein:
flavivirus

Front 56

only known human oncornavirinae

Back 56

Human T-cell Leukemia virus

Front 57

What CNS complications of Zoster?

Back 57

encephalitis

Front 58

What are the structural proteins of flaviviruses?

Back 58

E & M surface proteins
E protein – bind receptors and entry (M cleaved for maturation)
C to build nucleocapsids
-> basic, capsid

Front 59

What model of CJD is explained by the non-spontanious conversion of PrPc to PrpSc , but exposure to PrPSc caused the conversion?

Back 59

Refolding Model

Front 60

Virus family?

Eastern Equine Encephalitis (EEE)
Western Equine Encephalitis (WEE)
Rubella virus

Back 60

TOGAVIRUS

Front 61

Disease?

Neurosurgery, transplantation, brain-derived
Hormones

Back 61

Iatrogenic (iCJD)
CJD (creutzfeltd-jakob disease) is the most common TSE (transmissible spongiform encephalopathies) affecting humans

Front 62

Virus?
Ss(+)RNA enveloped, icosahedral
ABs to one serotype enhance virus uptake by phagocytic cells of another (instead of neutralizing)

Back 62

Dengue virus

Front 63

Virus and disease?
dsDNA linear, enveloped icosahedral

1. mental retardation
2. cerebral atrophy
3. Non-CNS abnormalities

Back 63

VZV
-part of herpesviruses
• Congenital Varicella

Front 64

Virus?
(+)ssRNA enveloped, icosahedral
• Resistant to low pH
• Grows at 37°C
• Resistant to detergents
• Site of primary infection is GI tract
• Fecal-oral transmission
• Murine encephalomyocarditis

Back 64

Cardiovirus
-part of picoravirus

Front 65

What change in protein is critical in the disease process of Transmissible Spongiform Encephalopathies (TSEs)?

Back 65

The change in conformation
of PrP from alpha-helical (PrPC) to beta-sheet (PrPSc)

Front 66

How does Cytomegalic inclusion disease present?

Back 66

mental retardation,
seizures,
blindness,
deafness,
death

Front 67

Virus?

(+) ssRNA enveloped, icosahedral
simple febrile headache to meningoencephalitis
Mild in children. The elders are at high risk for severe disease

Transmission by mosquito
Reservoir: Bird

Back 67

St. Louis encephalitis:
-part of flavivirus family

Different from West Nile virus bc West Nile virus sx include rash, lymphadenopathy and myalgias

Front 68

It is a 63-kDa protein, involved in RNA synthesis

Viral proteins
Picornovirus

Back 68

3D (RNA dependent RNA polymerase)

Viral non-structural proteins
Picornovirus

Front 69

Disease?

Autosomal dominant mutations in PRNP

Back 69

Familial (fCJD)
CJD is the most common TSE affecting humans

Front 70

Virus genera?

Hepatitis C, contains IRES

Back 70

Hepacivirus

Front 71

What virus and pt pop are associated with Progressive Multifocal Leukoencephalopathy ?

Back 71

JC virus and immunocomp pt

Front 72

What proteins are proteases for

1. Picronavirus
2. Flavivirus

Back 72

1. L, 2A, 3C
2. NS3

Front 73

What proteins are proteases for Picronavirus?

Back 73

L, 2A, 3C

Front 74

What proteins are proteases for Flavivirus?

Back 74

NS3

Front 75

Protein and virus?

translocated into the lumen and released from the
C’terminus of E by signal peptidase.

It is a membrane soluble haemagglutinin and elicits humoral immune responses and immunization with purified protein can be protective (IMP)

Back 75

NS1 protein
flavivirus

Front 76

Disease?

Origin from Scrapie (sheep)
- Infected sheep parts in animal-based cattle feed
-> cross “species barrier”
OR
Origin from spontaneous PrP mutation in cows -

Back 76

Bovine Spongiform Encephalitis
--> orginated from TSE = transmissible spongiform encephalopathies from prions

Front 77

How do congenital CMV infections other than Cytomegalic inclusion disease present?

Back 77

Hearing defects, intellectual impairment

Front 78

What is the cause of NV-CJD?

Back 78

Protease fingerpriting shows that NV-CJD prions resemble BSE prions NOT classical CJD prions

-> strongly suggesting transmission from cattle

Front 79

What type of CJD disease presents as follows:

dementia
ataxia
myclonus
visual disturbances

seen in ages 55 to 70

Cerebrum is the major target

Back 79

sCJD