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