Reddy: Viral CNS Infections II Flashcards
ARBOVIRUSES
Definition:
Definition: viruses that can be transmitted through the bite of infected insects
ARBOVIRUSES
Vectors (Carriers):
Primary Reservoir:
Hosts:
- Vectors (Carriers): mosquitoes, ticks and flies
- Primary Reservoir: birds
- Hosts: humans and other animals
ARBOVIRUSES
Viruses in this Category: (2)
- Flaviviridae
- Togaviridae
.
FLAVIVIRIDAE
Infect:
Infect: humans and animals
FLAVIVIRIDAE
Diseases: (6)
o Yellow Fever o West Nile Fever o Dengue Fever o Japanese Encephalitis o St. Louis Encephalitis o Tick-Borne Encephalitis
FLAVIVIRIDAE
General Symptoms:
o Severe headache
o Fever and chills
o N/V/D
FLAVIVIRIDAE
Genera (3):
o Flavivirus
o Pestivirus
o Hepacivirus
.
Flavivirus: (5)
Flavivirus: YFV, DFV, WNV, JE, SEV
Pestivirus: (2)
Pestivirus: Hog Cholera Virus, bovine viral diarrhea (no known human pathogens)
Hepacivirus:
Hepacivirus: Hep C Virus
FLAVIVIRIDAE
Shape:
enveloped icosahedral
Flaviviridae
Structural Proteins: Located where?
(3)
- 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)
Flaviviridae
Flavivirus
DNA type:
5’ cap?
poly a tail?
- Linear +ssRNA
- 5’ capped (methylated nucleotide cap)
- No 3’ poly A tail
Flaviviridae
Pestivirus
DNA type:
5’ cap?
poly a tail?
- Linear +ssRNA (longer than flavivirus)
- No 5’ cap; Internal ribosome entry site substitutes (IRES)
- No 3’ poly A tail
Flaviviridae
Hepacivirus
DNA type:
5’ cap?
poly a tail?
- Linear +ssRNA (longer than flavivirus)
- No 5’ cap; Internal ribosome entry site substitutes (IRES)
- No 3’ poly A tail
Flaviviridae
Lifecycle
Enters host cell by:
______ plays major role in attachment
Enters host cell by receptor mediated endocytosis
Envelope protein plays major role in attachment
Note: Cell surface receptors have not been well characterized
Flaviviridae
Dengue Virus 2 interacts with:
• DEN-2 (Dengue Virus 2): interacts with glycosaminoglycans and heparin sulfate
Flaviviridae
Antibody Dependent Enhancement (ADE) for Dengue Virus:
Antibody Dependent Enhancement (ADE) for Dengue Virus: additional mechanism of flaviviral binding
Flaviviridae
ADE
Ab raised against 1 serotype: (2 effects)
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
Flaviviridae
ADE
Virus bound to non-neutralizing Ab forms:
Virus bound to non-neutralizing Ab forms an infectious immune-complex that can enter macrophages and enhance viral infections
Flaviviridae
Lifecycle
After viral entry into cell, virion core:
C protein and ssRNA:
- After viral entry into cell, virion core disassembles in the cytoplasm (pH induced changed)
- C protein and ssRNA dissociate
Flaviviridae
Lifecycle
RNA translated into:
cleaved into :
RNA synthesis by:
encapsidation by:
- 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)
Flaviviridae
Lifecycle
Viral assembly in:
Virions accumulate in:
Transported to cell surface via:
- 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
Flaviviridae
Non-Structural Proteins
NS1:
NS2A and NS2B:
NS3:
- NS1: soluble hemagluttinin (elicits humoral immune responses)
- NS2A and NS2B: RNA synthesis
- NS3: viral protease
Flaviviridae
Non-Structural Proteins
NS4A and NS4B:
NS5:
- NS4A and NS4B: RNA replication
- NS5: RNA dependent RNA polymerase (RdRP)
Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus
Protease
Picronavirus
L, 2A, 3C
Flavivirus
NS3
Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus
RdRp
Picronavirus
3D
Flavivirus
NS5
Functionally Analogous Proteins (Important)
Picronavirus vs. Flavivirus
Capsid
Picronavirus
VP1, VP2, VP3, VP4
Flavivirus
C protein
Flaviviral Diseases: (6)
- West Nile Virus
- Yellow Fever
- Dengue Fever
- St. Louis Encephalitis
- Hepatitis C
West Nile Virus
Reservoir:
Vector:
Infects:
o Reservoir: birds
o Vector: mosquitoes, ticks
o Infects: humans, horses, bats, squirrels, and domestic rabbits
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
West Nile Virus
Treatment: (3)
- No vaccine
- Ribavirin (anti-viral)
- Mosquito control
Yellow Fever
Symptoms (6):
- High fever and chills
- Headache
- Vomiting
- Jaundice
- Hemorrhagic complications
- Renal failure
Yellow Fever
Treatment:
- Vaccine
* Mosquito control
Dengue Fever
Basics:
Symptoms: (3)
Basics: most prevalent among these diseases with a low mortality rate
Symptoms:
• Fever
• Headache
• Lumbosacral pain
Dengue Fever
Transmission:
Four Serotypes:
o Transmission: person to person via mosquitoes
o Four Serotypes: no cross reactive immunity (remember ADE)
Dengue Fever
Diseases:
Treatment:
o Diseases: Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS)
o Treatment: only control of Arthropod vectors
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
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
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
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
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
Togavirus
Viruses in this Class: (3)
- EEE
- WEE
- Rubella virus
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
Togaviral Diseases:
Eastern Equine Encephalitis (EEE)
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
Eastern Equine Encephalitis (EEE)
Symptoms: (6)
- Fever
- General muscle pains
- Severe headache
- Permanent brain damage
- Seizures
- Coma
Eastern Equine Encephalitis (EEE)
Transmission:
Pathology:
o Transmission: infected saliva through mosquito bite
o Pathology: small hemorrhages in the brain and extensive neural damage
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
Rhabdovirus
Genome:
Contains:
- Genome: -ssRNA
o Contains an RNA dependent viral RNA transcriptase
Rhabdovirus
Infectious Component:
Replication:
- Infectious Component: ribonucleoprotien (RNP) is the most infectious part of the virus
- Replication: cytoplasm
.
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
Rhabdovirus
Symptoms
Early:
o Non-specific, flu like symptoms
o Headache
o Difficulty swallowing
o Hydrophobia
Rhabdovirus
Symptoms
Late:
o Cerebral dysfunction o Anxiety o Confusion o Agitation o Hallucinations o Insomnia
Rhabdovirus
Pathology:
Pathology: cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells; neuronal necrosis can also result
Rhabdovirus
Location of Negri bodies:
o Pyramidal cells of hippocampus
o Neurons of cortex
o Outer regions of CNS (including spinal ganglia)
Rhabdovirus
Diagnosis:
Standard Test:
• Diagnosis: no test available to rule out rabies in humans with certainty
- Standard Test: Fluorescent Ab Assay
Rhabdovirus
Diagnosis
Others:
o Electron microscopy
o Histologic examination
o Immunohistochemistry (IHC)
o RT-PCR
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)
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
Rhabdovirus
Prevention:
Prevention: vaccination of wild and domestic animals
