Reddy: Viral CNS Infections II Flashcards

1
Q

ARBOVIRUSES

Definition:

A

Definition: viruses that can be transmitted through the bite of infected insects

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2
Q

ARBOVIRUSES

Vectors (Carriers):
Primary Reservoir:
Hosts:

A
  • Vectors (Carriers): mosquitoes, ticks and flies
  • Primary Reservoir: birds
  • Hosts: humans and other animals
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3
Q

ARBOVIRUSES

Viruses in this Category: (2)

A
  • Flaviviridae
  • Togaviridae

.

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4
Q

FLAVIVIRIDAE

Infect:

A

Infect: humans and animals

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5
Q

FLAVIVIRIDAE

Diseases: (6)

A
o	Yellow Fever
o	West Nile Fever
o	Dengue Fever
o	Japanese Encephalitis
o	St. Louis Encephalitis 
o	Tick-Borne Encephalitis
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6
Q

FLAVIVIRIDAE

General Symptoms:

A

o Severe headache
o Fever and chills
o N/V/D

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7
Q

FLAVIVIRIDAE

Genera (3):

A

o Flavivirus
o Pestivirus
o Hepacivirus

.

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8
Q

Flavivirus: (5)

A

Flavivirus: YFV, DFV, WNV, JE, SEV

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9
Q

Pestivirus: (2)

A

Pestivirus: Hog Cholera Virus, bovine viral diarrhea (no known human pathogens)

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10
Q

Hepacivirus:

A

Hepacivirus: Hep C Virus

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11
Q

FLAVIVIRIDAE

Shape:

A

enveloped icosahedral

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12
Q

Flaviviridae
Structural Proteins: Located where?
(3)

A
  • Structural Proteins: located close to the 5’ end (N’ ¼ of the polyprotein)
    1. Envelope (essential for host cell receptor binding)
    2. PrM (M protein is cleaved from this precursor upon maturation of virion- maturation signal)
    3. C (nucleocapsid)
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13
Q

Flaviviridae
Flavivirus

DNA type:
5’ cap?
poly a tail?

A
  • Linear +ssRNA
  • 5’ capped (methylated nucleotide cap)
  • No 3’ poly A tail
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14
Q

Flaviviridae
Pestivirus

DNA type:
5’ cap?
poly a tail?

A
  • Linear +ssRNA (longer than flavivirus)
  • No 5’ cap; Internal ribosome entry site substitutes (IRES)
  • No 3’ poly A tail
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15
Q

Flaviviridae
Hepacivirus

DNA type:
5’ cap?
poly a tail?

A
  • Linear +ssRNA (longer than flavivirus)
  • No 5’ cap; Internal ribosome entry site substitutes (IRES)
  • No 3’ poly A tail
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16
Q

Flaviviridae
Lifecycle

Enters host cell by:
______ plays major role in attachment

A

Enters host cell by receptor mediated endocytosis

Envelope protein plays major role in attachment

Note: Cell surface receptors have not been well characterized

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17
Q

Flaviviridae

Dengue Virus 2 interacts with:

A

• DEN-2 (Dengue Virus 2): interacts with glycosaminoglycans and heparin sulfate

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18
Q

Flaviviridae

Antibody Dependent Enhancement (ADE) for Dengue Virus:

A

Antibody Dependent Enhancement (ADE) for Dengue Virus: additional mechanism of flaviviral binding

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19
Q

Flaviviridae
ADE
Ab raised against 1 serotype: (2 effects)

A

Ab raised against 1 serotype both fails to neutralize other viral serotypes AND enhances infection by providing efficient means of viral uptake by phagocytic cells

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20
Q

Flaviviridae
ADE
Virus bound to non-neutralizing Ab forms:

A

Virus bound to non-neutralizing Ab forms an infectious immune-complex that can enter macrophages and enhance viral infections

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21
Q

Flaviviridae
Lifecycle

After viral entry into cell, virion core:
C protein and ssRNA:

A
  • After viral entry into cell, virion core disassembles in the cytoplasm (pH induced changed)
  • C protein and ssRNA dissociate
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22
Q

Flaviviridae
Lifecycle

RNA translated into:
cleaved into :

RNA synthesis by:
encapsidation by:

A
  • RNA translated into viral polyprotein → cleaved into 10 mature proteins (10 structural and 7 non-structural)
  • RNA synthesis by RdRp + encapsidation by C protein (nucleocapsid)
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23
Q

Flaviviridae
Lifecycle

Viral assembly in:
Virions accumulate in:
Transported to cell surface via:

A
  • Viral assembly in cytoplasm → maturation at internal membranes of rER or Golgi
  • Virions accumulate in membrane bound vesicles
  • Transported to cell surface via secretory pathway → exocytosis
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24
Q

Flaviviridae
Non-Structural Proteins

NS1:
NS2A and NS2B:
NS3:

A
  • NS1: soluble hemagluttinin (elicits humoral immune responses)
  • NS2A and NS2B: RNA synthesis
  • NS3: viral protease
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25
Q

Flaviviridae
Non-Structural Proteins

NS4A and NS4B:
NS5:

A
  • NS4A and NS4B: RNA replication

- NS5: RNA dependent RNA polymerase (RdRP)

26
Q

Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus

Protease

A

Picronavirus
L, 2A, 3C

Flavivirus
NS3

27
Q

Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus

RdRp

A

Picronavirus
3D

Flavivirus
NS5

28
Q

Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus

Capsid

A

Picronavirus
VP1, VP2, VP3, VP4

Flavivirus
C protein

29
Q

Flaviviral Diseases: (6)

A
  • West Nile Virus
  • Yellow Fever
  • Dengue Fever
  • St. Louis Encephalitis
  • Hepatitis C
30
Q

West Nile Virus

Reservoir:
Vector:
Infects:

A

o Reservoir: birds
o Vector: mosquitoes, ticks
o Infects: humans, horses, bats, squirrels, and domestic rabbits

31
Q

West Nile Virus
Human Pathogenesis

Onset:
Symptoms: (big list)

A

Basics: abrupt onset febrile, flu-like illness

Symptoms:
➢	Moderate to high fever
➢	Headache
➢	Sore throat
➢	Back ache
➢	Fatigue 
➢	Rash
➢	Lymphadenopathy
➢	Myalgias
➢	Acute aseptic meningitis or encephalitis
32
Q

West Nile Virus

Treatment: (3)

A
  • No vaccine
  • Ribavirin (anti-viral)
  • Mosquito control
33
Q

Yellow Fever

Symptoms (6):

A
  • High fever and chills
  • Headache
  • Vomiting
  • Jaundice
  • Hemorrhagic complications
  • Renal failure
34
Q

Yellow Fever

Treatment:

A
  • Vaccine

* Mosquito control

35
Q

Dengue Fever

Basics:
Symptoms: (3)

A

Basics: most prevalent among these diseases with a low mortality rate

Symptoms:
• Fever
• Headache
• Lumbosacral pain

36
Q

Dengue Fever

Transmission:
Four Serotypes:

A

o Transmission: person to person via mosquitoes

o Four Serotypes: no cross reactive immunity (remember ADE)

37
Q

Dengue Fever

Diseases:
Treatment:

A

o Diseases: Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS)
o Treatment: only control of Arthropod vectors

38
Q

St. Louis Encephalitis

A leading cause of:
Transmission:
Reservoir:

A

Basics: a leading cause of epidemic flaviviral encephalitis in the US

Transmission: by mosquito

Reservoir: birds

39
Q

St. Louis Encephalitis

Symptoms:
in children?
Elderly:

A

o Symptoms: range from simple febrile headache to meningoencephalitis
• Mild in children
• Elderly at high risk for severe disease

40
Q

Hepatitis C
Hepatitis:
Transmission:

A

o Hepatitis: inflammation of the liver leading to chronic inflammation and cirrhosis (scarring)
o Transmission: via blood or infected syringes, tattooing and body piercing also possible

41
Q

Hepatitis C
Treatment

IFN:
IFN-alpha:
IFN-beta:
IFN-gamma:

A

IFN: cytokines with antiviral response (normally synthesized by the host)

  • IFN-alpha: produced by leukocytes
  • IFN-beta: produced by fibroblasts and epithelial cells
  • IFN-gamma: produced by T cells
42
Q

Hepatitis C

Function of IFN:
Efficacy:
Often combined with:

A

Function of IFN: induces the synthesis of IFN response genes that regulate viral proteins at the transcriptional and translational level (inhibit viral proteins)

Efficacy: only in 15% of patients
➢ Often combined with Ribavirin (Rebetron) for the treatment of relapsed patients

43
Q

Togavirus

Viruses in this Class: (3)

A
  • EEE
  • WEE
  • Rubella virus
44
Q

Togavirus

Structure:
Non-Structural Proteins:
Structural Proteins (Capsid and Envelope):

A
  • Structure: enveloped
    o Non-Structural Proteins: 5’ end of genome
    o Structural Proteins (Capsid and Envelope): 3’ end of genome
  • Genome: +ssRNA
  • Replication: cytoplasm
45
Q

Togaviral Diseases:

A

Eastern Equine Encephalitis (EEE)

46
Q

Eastern Equine Encephalitis (EEE)

Basics:
Reservoir:
Carrier:
Infects:

A

o Basics: rare disease but very fatal
o Reservoir: birds (marsh birds)
o Carrier: mosquitoes
o Infects: humans, horses, birds (ie. pheasants), quail and ostriches

47
Q

Eastern Equine Encephalitis (EEE)

Symptoms: (6)

A
  • Fever
  • General muscle pains
  • Severe headache
  • Permanent brain damage
  • Seizures
  • Coma
48
Q

Eastern Equine Encephalitis (EEE)

Transmission:
Pathology:

A

o Transmission: infected saliva through mosquito bite

o Pathology: small hemorrhages in the brain and extensive neural damage

49
Q

Rhabdovirus
Transmission:
Structure:

A
  • Transmission: from animals to humans (zoonoses) through animal bite (infected saliva)
  • Structure: bullet shaped with external glycoprotein coat and peripheral matrix protein
50
Q

Rhabdovirus
Genome:
Contains:

A
  • Genome: -ssRNA

o Contains an RNA dependent viral RNA transcriptase

51
Q

Rhabdovirus

Infectious Component:
Replication:

A
  • Infectious Component: ribonucleoprotien (RNP) is the most infectious part of the virus
  • Replication: cytoplasm

.

52
Q

Rhabdovirus
Spread and Multiplication

Via:
Incubation time:

A

• Spread and Multiplication:

  • Via bite and virus-containing saliva of infected host
  • Incubation time up to 12 months; quickly advances to PNS (submaxillary salivary glands) and CNS
53
Q

Rhabdovirus
Symptoms

Early:

A

o Non-specific, flu like symptoms
o Headache
o Difficulty swallowing
o Hydrophobia

54
Q

Rhabdovirus
Symptoms

Late:

A
o	Cerebral dysfunction
o	Anxiety 
o	Confusion 
o	Agitation
o	Hallucinations
o	Insomnia
55
Q

Rhabdovirus

Pathology:

A

Pathology: cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells; neuronal necrosis can also result

56
Q

Rhabdovirus

Location of Negri bodies:

A

o Pyramidal cells of hippocampus
o Neurons of cortex
o Outer regions of CNS (including spinal ganglia)

57
Q

Rhabdovirus

Diagnosis:
Standard Test:

A

• Diagnosis: no test available to rule out rabies in humans with certainty
- Standard Test: Fluorescent Ab Assay

58
Q

Rhabdovirus
Diagnosis

Others:

A

o Electron microscopy
o Histologic examination
o Immunohistochemistry (IHC)
o RT-PCR

59
Q

Rhabdovirus
Vaccine

Important point:
Pre-exposure vaccine:

A
  • Important point: there is NO treatment for rabies once symptoms of the disease appear
  • Pre-exposure vaccine: recommended for high risk groups (vets, animal handlers, lab workers)
60
Q

Rhabdovirus
Post-Exposure Treatment

Local Wound Treatment:
Passive Immunization:
Vaccination:

A
  • Local Wound Treatment: wash wound thoroughly with soap and water and seek medical attention immediately
  • Passive Immunization: human rabies immune globulins (HRIG) collected from immunized persons and administered to people exposed to rabies
  • Vaccination: immunize with human diploid cell rabies vaccine (HDCV) which has inactivated virus
61
Q

Rhabdovirus

Prevention:

A

Prevention: vaccination of wild and domestic animals