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Micro Exam 3 > Reddy: Viral CNS Infections I > Flashcards

Reddy: Viral CNS Infections I Flashcards

1
Q

RNA Viruses: (7)

A
  • Picornaviruses
  • Flaviviruses
  • Togaviruses
  • Reoviruses
  • Rhabdoviruses
  • Bunyaviruses
  • Retroviruses
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2
Q

Picornaviruses: (3)

A

Polio, Coxsackie, Hep A

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3
Q

Flaviviruses: (3)

A

West Nile Virus, Yellow Fever Virus, dengue

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4
Q

Togaviruses: (3)

A

Western Equine Encephalitis, Eastern Equine Encephalitis, Venezuelan Equine Encephalitis

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5
Q

Reoviruses: (1)

A

Colorado Tick Fever

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6
Q

Rhabdoviruses:

A

Rabies

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7
Q

Bunyaviruses:

A

California Encephalitis

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8
Q

Retroviruses:

A

HTLV-1, HIV

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9
Q

Herpesviruses: (3)

A

HSV-1, HSV-2, VZV

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10
Q

PICORNAVIRUSES

• Basics:

A
  • Small RNA genome

- 5 genera based on physical properties and nucleotide sequence homology

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11
Q

Picornaviruses

Enterovirus:

A

Diseases of human (and other) alimentary tract (Polio, Coxsackie A and B, ECHO)

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12
Q

Picornaviruses

Rhinovirus:

A

Nasopharyngeal region (common cold)

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13
Q

Picornaviruses

Aphthovirus:

A

Foot and mouth disease of cloven footed animals

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14
Q

Picornaviruses

Hepatovirus:

A

Human hepatitis A virus

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15
Q

Enterovirus, Hepatovirus and Cardiovirus

Structure:
Growth:

A 
o	Structure: no envelope
o	Growth:
•	Resistant to low pH
•	Grows at 37 degrees C
•	Resistant to detergents (no envelope)
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16
Q

Enterovirus, Hepatovirus and Cardiovirus

Transmission:
Primary Infection:

A

o Transmission: fecal-oral

o Primary Infection: GI tract

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17
Q

Enterovirus, Hepatovirus and Cardiovirus

CNS Infections:
Progression to CNS infection depends on:

A

o CNS Infections: result in paralysis and encephalitis

• Progression to CNS infection depends on viral inoculums, viral infectivity and host immunity

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18
Q

Rhinovirus and Aphthovirus

Growth:

A
  • Labile at low pH

* Grow at 33 degrees C

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19
Q

Rhinovirus and Aphthovirus
Transmission:
Primary Infection:

A

o Transmission: aerosols

o Primary Infection: upper respiratory tract

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20
Q

Picornaviruses
Capsid Structure

Enveloped?
What is Icosahedral nucleocapsid made of?

A

o Non-enveloped

o Icosahedral nucleocapsid (made of VP1, VP2, VP3 and VP4)

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21
Q

Picornaviruses
Capsid Structure

Protomer:
Full Capsid:

A
  • Protomer: basic building block of the capsid; has one copy each of VP1, VP2, VP3 and VP4
  • Full Capsid: consists of 60 of the above protomers
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22
Q

Picornaviruses

Genome Structure:
5’ End:

A

Genome Structure: +ssRNA

5’ End
• Capsid (structural protein) encoded by 5’ end
• Replication and translation controlled by long 5’ non-coding region (NCR)
➢ Has a clover-leaf secondary structure (Internal Ribosome Entry Site/IRES)
• Covalently linked to VPg protein

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23
Q

Picornaviruses
Genome Structure
3’ End:

A

o 3’ End:
• Protease (and other enzymes) encoded by 3’ end
• RNA synthesis controlled by a short 3’ NCR with poly A tail

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24
Q

Picornaviruses

Polyprotein:

A
  • A single open reading frame codes for a single polypeptide divided into 3 regions (P1, P2, P3)
  • Cleavage leads to 11-12 proteins
25
Picornaviruses | Regions:
P1,2,3
26
P1:
P1: encodes viral capsid proteins (VP1, VP2, VP3, VP4)
27
P2/P3 | Encode proteins involved in protein processing:
Encode proteins involved in protein processing (2A, 3C, 3CD)
28
P2/P3 | Encode proteins involved in genome replication:
Encode proteins involved in genome replication (2B, 2C, 3AB, 3B, 3CD, 3D)
29
Aphthoviruses and Cardioviruses encode:
Aphthoviruses and Cardioviruses: also encode a leader protein (L) before he P1 region
30
Picornaviruses Ingestion: Target Site:
- Ingestion: into GI tract (fecal-oral spread) | - Target Site: lymphoid tissue of the oropharynx and gut
31
Picornaviruses Viral Replication:
- Viral Replication: occurs in oropharynx and/or small intestine o Tonsils, cervical nodes, Peyer’s patches, mesenteric LNs
32
Picornaviruses Initial Viremia Transient vs Major:
Appearance of Ab leads to disappearance of virus and transient viremia Without Ab, virus localizes in various organs leading to major viremia
33
Picornaviruses Major Viremia: Viral production mainly in: In severe illness, ____ can result
- Major Viremia: can invade the CNS o Viral production mainly in the grey matter (motor neurons of the anterior horns of the spinal cord and brain stem) o In severe illness, paralysis can result
34
Picornaviruses | Excretion:
- Virus is excreted in the feces .
35
Picornaviruses Replication Cycle part 1 Attachment of virus to cellular R via _____ (can directly penetrate cell or be taken in via endocytosis) _______ of the genome (____ released into cytoplasm Viral translation to _______ _______ processing
o Attachment of virus to cellular R via VP1 (can directly penetrate cell or be taken in via endocytosis) o Uncoating of the genome (RNA released into cytoplasm) o Viral translation to polyprotein o Protein processing (cleavage of polyprotein)
36
Picornaviruses Replication Cycle part 2 Synthesis of RNA in membrane vesicles and copying of ___ to ___ Copying to multiple: Additional proteins formed from: _____ of RNA and viral protein assembly ' Release of new viral particles by _____
Synthesis of RNA in membrane vesicles and copying of +ssRNA to –ssRNA (used as template) Copying to multiple +ssRNA from the –ssRNA templates Additional proteins formed from new +ssRNA Encapsidation of RNA and viral protein assembly Release of new viral particles by cell lysis
37
Picornaviruses Host Receptors Some viruses use a single type of receptor: (3)
Some viruses use a single type of receptor (poliovirus, rhinovirus attach to Pvr)
38
Picornaviruses Host Receptors Some also require a co-receptor:
- Others also require a co-receptor (coxsackivirus A21 binds CD55 but also requires ICAM-1)
39
Picornaviruses Host Protein Synthesis Shut Off Basics:
• Host Protein Synthesis Shut Off: | - Basics: shut off host cell genes without affecting synthesis of their own proteins
40
Picornaviruses Mechanism: Enterovirus/Rhinovirus: Aphthovirus:
- Mechanism: cleave cellular protein eIF-4G, resulting in protein synthesis shut off o Enterovirus/Rhinovirus: do so using viral 2A protease o Aphthovirus: does so using L protein
41
Picornaviruses Viral Non-Structural Proteins 2A: 2B:
- 2A: viral protease (polyprotein cleavage) | - 2B: enhances vesicle formation in host (site of RNA synthesis)
42
Picornaviruses Viral Non-Structural Proteins 2C: 3AB:
- 2C: RNA helicase (unwinds folded RNA during replication) | - 3AB: stimulates 3D polymerase activity and proteolytic activity of 3CD proteinase
43
Picornaviruses Viral Non-Structural Proteins 3C: 3D: VPg:
- 3C: viral protease - 3D: RNA dependent RNA polymerase (RNA synthesis) - VPg: provides poly U primer (primes RNA synthesis)
44
Picornaviral Diseases: (4)
- Poliovirus - Coxsackie Viruses (A and B) - Rhinoviruses - Aphthoviruses
45
Poliovirus Causes: Progression: Pathogenesis:
Causes: poliomyelitis (most severe disease caused by picornaviruses) • 3 types of poliovirus, with most cases of disease being caused by type 1 Progression: only 1% of infected individuals progress to poliomyelitis Pathogenesis: flaccid paralysis from destruction of motor neurons in anterior horn of spinal cord
46
Poliovirus Last documented case: IPV/Salk (inactivated): Sabin/OPV (live, attenuated):
o Last documented case in the US: 1979 (due to vaccination) • IPV/Salk (inactivated): less GI immunity and duration not known with certainty • Sabin/OPV (live, attenuated): highly effective with life-long immunity (but risk of reversion)
47
Poliovirus Eradication:
Eradication: possible due to vaccination (stable and long lasting immunity) and the fact that humans are the only reservoirs for poliovirus
48
Coxsackie Viruses (A and B) Who is at risk? Group A:
Children are the at risk population o Group A: • Aseptic meningitis (headache, stiff neck, fever) • Herpangina (sudden onset fever with ulcers on tonsils and palate) • Hand-foot-mouth disease (A16 specifically)
49
``` Coxsackie Viruses (A and B) Group B: ```
o Group B: | • Aseptic meningitis (headache, stiff neck, fever)
50
Rhinoviruses Causes: Treatment:
o Causes: common cold | o Treatment: pleconaril (also used against enteroviruses); no prospects for vaccines
51
Aphthoviruses Causes: Control:
o Causes: foot and mouth disease in animals o Control: vaccination or slaughter of infected animals • Note: vaccination is effective against symptoms but NOT against transmission to other animals
52
HIV Neurological Complications: Cell Tropism:
Neurological Complications: common among AIDS patients o HIV found in CSF and brains of HIV patients (HIV Associated Dementia) Cell Tropism: o T cell tropic viruses o Macrophage tropic viruses o Neurotropic viruses (still unclear)
53
Potential Targets for HIV-1: (4)
o Entry o Reverse Transcriptase (RT): • NRTI: incorporate into growing strand of DNA and terminate DNA synthesis ➢ Zidovudine (AZT-thymidine analog), Didanosine, Zalcitabine, Stavudine, Lamivudine • NNRTI: directly interact with RT enzyme to inhibit function ➢ Nevirapine, Delavirdine o Integrase o Protease: cleaves polyproteins into functional protein • Protease Inhibitors: Ritonavir, Indinavir, Saquinovir, Nelfinavir
54
HAART:
- HAART: highly active anti-retroviral treatment o Does not provide full protection against neurological damage in AIDs (because the BBB is only partially permeable to anti-retroviral agents)
55
Oncornaviridae: What is the only known human virus in this class?
HTLV
56
HTLV | Diseases:
o Adult T cell leukeumia (ATL) | o Tropical spastic paraparesis/HTLV-1 associated myelopathy (neurological disease)
57
HTLV | Transmission:
o Mother to child (breast-feeding) o Sex o Blood transfusion o IV drug use
58
HTLV Prevalent Areas: Treatment:
- Prevalent Areas: Southwest Japan, Carribean basin, parts of South America, Central and West Africa ``` - Treatment: no specific and effective treatments o IFN-alpha + Zidovudine o Chemotherapy (limited success) o Zidovudine + Danazol + Vitamin C (temporary relief from TSP) ```

Micro Exam 3 (11 decks)

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