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

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
Flaviviridae Non-Structural Proteins NS4A and NS4B: NS5:
- NS4A and NS4B: RNA replication | - NS5: RNA dependent RNA polymerase (RdRP)
26
Functionally Analogous Proteins (Important) Picronavirus vs. Flavivirus Protease
Picronavirus L, 2A, 3C Flavivirus NS3
27
Functionally Analogous Proteins (Important) Picronavirus vs. Flavivirus RdRp
Picronavirus 3D Flavivirus NS5
28
Functionally Analogous Proteins (Important) Picronavirus vs. Flavivirus Capsid
Picronavirus VP1, VP2, VP3, VP4 Flavivirus C protein
29
Flaviviral Diseases: (6)
- West Nile Virus - Yellow Fever - Dengue Fever - St. Louis Encephalitis - Hepatitis C
30
West Nile Virus Reservoir: Vector: Infects:
o Reservoir: birds o Vector: mosquitoes, ticks o Infects: humans, horses, bats, squirrels, and domestic rabbits
31
West Nile Virus Human Pathogenesis Onset: Symptoms: (big list)
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
West Nile Virus | Treatment: (3)
* No vaccine * Ribavirin (anti-viral) * Mosquito control
33
Yellow Fever | Symptoms (6):
* High fever and chills * Headache * Vomiting * Jaundice * Hemorrhagic complications * Renal failure
34
Yellow Fever | Treatment:
* Vaccine | * Mosquito control
35
Dengue Fever Basics: Symptoms: (3)
Basics: most prevalent among these diseases with a low mortality rate Symptoms: • Fever • Headache • Lumbosacral pain
36
Dengue Fever Transmission: Four Serotypes:
o Transmission: person to person via mosquitoes | o Four Serotypes: no cross reactive immunity (remember ADE)
37
Dengue Fever Diseases: Treatment:
o Diseases: Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) o Treatment: only control of Arthropod vectors
38
St. Louis Encephalitis A leading cause of: Transmission: Reservoir:
Basics: a leading cause of epidemic flaviviral encephalitis in the US Transmission: by mosquito Reservoir: birds
39
St. Louis Encephalitis Symptoms: in children? Elderly:
o Symptoms: range from simple febrile headache to meningoencephalitis • Mild in children • Elderly at high risk for severe disease
40
Hepatitis C Hepatitis: Transmission:
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
Hepatitis C Treatment IFN: IFN-alpha: IFN-beta: IFN-gamma:
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
Hepatitis C Function of IFN: Efficacy: Often combined with:
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
Togavirus | Viruses in this Class: (3)
- EEE - WEE - Rubella virus
44
Togavirus Structure: Non-Structural Proteins: Structural Proteins (Capsid and Envelope):
- 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
Togaviral Diseases:
Eastern Equine Encephalitis (EEE)
46
Eastern Equine Encephalitis (EEE) Basics: Reservoir: Carrier: Infects:
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
Eastern Equine Encephalitis (EEE) Symptoms: (6)
* Fever * General muscle pains * Severe headache * Permanent brain damage * Seizures * Coma
48
Eastern Equine Encephalitis (EEE) Transmission: Pathology:
o Transmission: infected saliva through mosquito bite | o Pathology: small hemorrhages in the brain and extensive neural damage
49
Rhabdovirus Transmission: Structure:
- Transmission: from animals to humans (zoonoses) through animal bite (infected saliva) - Structure: bullet shaped with external glycoprotein coat and peripheral matrix protein
50
Rhabdovirus Genome: Contains:
- Genome: -ssRNA | o Contains an RNA dependent viral RNA transcriptase
51
Rhabdovirus Infectious Component: Replication:
- Infectious Component: ribonucleoprotien (RNP) is the most infectious part of the virus - Replication: cytoplasm .
52
Rhabdovirus Spread and Multiplication Via: Incubation time:
• 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
Rhabdovirus Symptoms Early:
o Non-specific, flu like symptoms o Headache o Difficulty swallowing o Hydrophobia
54
Rhabdovirus Symptoms Late:
``` o Cerebral dysfunction o Anxiety o Confusion o Agitation o Hallucinations o Insomnia ```
55
Rhabdovirus | Pathology:
Pathology: cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells; neuronal necrosis can also result
56
Rhabdovirus Location of Negri bodies:
o Pyramidal cells of hippocampus o Neurons of cortex o Outer regions of CNS (including spinal ganglia)
57
Rhabdovirus Diagnosis: Standard Test:
• Diagnosis: no test available to rule out rabies in humans with certainty - Standard Test: Fluorescent Ab Assay
58
Rhabdovirus Diagnosis Others:
o Electron microscopy o Histologic examination o Immunohistochemistry (IHC) o RT-PCR
59
Rhabdovirus Vaccine Important point: Pre-exposure vaccine:
- 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
Rhabdovirus Post-Exposure Treatment Local Wound Treatment: Passive Immunization: Vaccination:
- 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
Rhabdovirus | Prevention:
Prevention: vaccination of wild and domestic animals

Micro Exam 3 (11 decks)

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