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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
Q

Picornaviruses

Regions:

A

P1,2,3

26
Q

P1:

A

P1: encodes viral capsid proteins (VP1, VP2, VP3, VP4)

27
Q

P2/P3

Encode proteins involved in protein processing:

A

Encode proteins involved in protein processing (2A, 3C, 3CD)

28
Q

P2/P3

Encode proteins involved in genome replication:

A

Encode proteins involved in genome replication (2B, 2C, 3AB, 3B, 3CD, 3D)

29
Q

Aphthoviruses and Cardioviruses encode:

A

Aphthoviruses and Cardioviruses: also encode a leader protein (L) before he P1 region

30
Q

Picornaviruses

Ingestion:
Target Site:

A
  • Ingestion: into GI tract (fecal-oral spread)

- Target Site: lymphoid tissue of the oropharynx and gut

31
Q

Picornaviruses

Viral Replication:

A
  • Viral Replication: occurs in oropharynx and/or small intestine
    o Tonsils, cervical nodes, Peyer’s patches, mesenteric LNs
32
Q

Picornaviruses
Initial Viremia

Transient vs Major:

A

Appearance of Ab leads to disappearance of virus and transient viremia

Without Ab, virus localizes in various organs leading to major viremia

33
Q

Picornaviruses
Major Viremia:
Viral production mainly in:
In severe illness, ____ can result

A
  • 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
Q

Picornaviruses

Excretion:

A
  • Virus is excreted in the feces

.

35
Q

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

A

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
Q

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 _____

A

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
Q

Picornaviruses
Host Receptors
Some viruses use a single type of receptor: (3)

A

Some viruses use a single type of receptor (poliovirus, rhinovirus attach to Pvr)

38
Q

Picornaviruses
Host Receptors
Some also require a co-receptor:

A
  • Others also require a co-receptor (coxsackivirus A21 binds CD55 but also requires ICAM-1)
39
Q

Picornaviruses
Host Protein Synthesis Shut Off
Basics:

A

• Host Protein Synthesis Shut Off:

- Basics: shut off host cell genes without affecting synthesis of their own proteins

40
Q

Picornaviruses

Mechanism:
Enterovirus/Rhinovirus:
Aphthovirus:

A
  • 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
Q

Picornaviruses
Viral Non-Structural Proteins

2A:
2B:

A
  • 2A: viral protease (polyprotein cleavage)

- 2B: enhances vesicle formation in host (site of RNA synthesis)

42
Q

Picornaviruses
Viral Non-Structural Proteins

2C:
3AB:

A
  • 2C: RNA helicase (unwinds folded RNA during replication)

- 3AB: stimulates 3D polymerase activity and proteolytic activity of 3CD proteinase

43
Q

Picornaviruses
Viral Non-Structural Proteins

3C:
3D:
VPg:

A
  • 3C: viral protease
  • 3D: RNA dependent RNA polymerase (RNA synthesis)
  • VPg: provides poly U primer (primes RNA synthesis)
44
Q

Picornaviral Diseases: (4)

A
  • Poliovirus
  • Coxsackie Viruses (A and B)
  • Rhinoviruses
  • Aphthoviruses
45
Q

Poliovirus

Causes:
Progression:
Pathogenesis:

A

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
Q

Poliovirus

Last documented case:
IPV/Salk (inactivated):
Sabin/OPV (live, attenuated):

A

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
Q

Poliovirus

Eradication:

A

Eradication: possible due to vaccination (stable and long lasting immunity) and the fact that humans are the only reservoirs for poliovirus

48
Q

Coxsackie Viruses (A and B)
Who is at risk?
Group A:

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
Q 
Coxsackie Viruses (A and B)
Group B:
A

o Group B:

• Aseptic meningitis (headache, stiff neck, fever)

50
Q

Rhinoviruses

Causes:
Treatment:

A

o Causes: common cold

o Treatment: pleconaril (also used against enteroviruses); no prospects for vaccines

51
Q

Aphthoviruses

Causes:
Control:

A

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
Q

HIV

Neurological Complications:
Cell Tropism:

A

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
Q

Potential Targets for HIV-1: (4)

A

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
Q

HAART:

A
  • 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
Q

Oncornaviridae: What is the only known human virus in this class?

A

HTLV

56
Q

HTLV

Diseases:

A

o Adult T cell leukeumia (ATL)

o Tropical spastic paraparesis/HTLV-1 associated myelopathy (neurological disease)

57
Q

HTLV

Transmission:

A

o Mother to child (breast-feeding)
o Sex
o Blood transfusion
o IV drug use

58
Q

HTLV

Prevalent Areas:
Treatment:

A
  • 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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