Viral CNS infections Flashcards
What are the three types of virus within the picornavirus family?
- Enterovirus - i.e. poliovirus / coxsackievirus
- Rhinovirus
- Hepatovirus - i.e. Hep A
What is the primary structural difference between Entervirus/Hepatovirus and Rhinovirus?
Entero/Hepato are resistant to low pH and grow optimally at normally body temp (can pass thru stomach and live in GI tract)
Rhinoviruses are labile to low pH, but grow at 33 C in the URT and have aerosolic transmission
What is the present in the 5’ UTR (untranslated region) of picornaviruses?
“Clover leaf” called Internal Ribosome Entry Site (IRES) which takes the place of the 5’ cap of RNA and controls translation
What is the VPg protein?
Protein linking to the 5’ end of viral RNA of picornaviruses, provides the polyU primer for RNA synthesis
What is the function of the 3’-UTR in picornaviruses
Controls RNA synthesis
What are P1-P3 and what is their general function?
Picornaviruses synthesize all their proteins from one polyprotein via open reading frame, which are then cleaved (total of 11-12 proteins)
P1: Viral capsid proteins
P2: Protein processing proteins
P3: Genome replication proteins
What receptor do picornaviruses use, and specifically what receptor does polio use?
Wide variety of host cell surface receptors
Polioviruses use a single Pvr (polio virus receptor)
Where do picornaviruses replicate?
In the cytoplasm
What is the mechanism of RNA replication in picornaviruses?
Use +RNA genome to make -RNA strand from which multiple +RNA’s are made (via RNA-dependent RNA polymerase)
What protein encodes the RNA-dependent RNA polymerase in picornaviruses?
3D
What must the 3D protein work in conjunction with to function?
VPg - which provides the polyU primer for RNA synthesis
What three loci encode viral proteases?
L, 2A, and 3C
Where does poliovirus try to replicate?
The lymphoid tissue of oropharynx and gut - i.e. tonsils, cervical nodes, Peyer’s patches, mesenteric nodes
What is the difference between transient and major viremia?
Transient - virus momentary passes through bloodstream to reach other lymphoid tissue
Major - no protective antibody is made, allowing for virus to reach various organs and ultimately invade CNS
What part of the CNS does polioviral replication occur? What can this lead to?
Mainly gray matter, especially the motor neurons in the anterior horn of the spinal corn. In severe cases, this can lead to flaccid paralysis
Where does poliovirus get excreted?
In the feces
What are the two types of poliovirus vaccines and which one is more effective in elliciting a long-term response?
- Salk - inactivated - given intramuscularly
2. Sabin - live, attenuated - given orally and most protective / longest term response
Why is eradication of polio very possible?
Humans are the only reservoir, vaccine is stable and easy to transfer with long-lasting immunity
What are three conditions caused by Cocksackie A virus?
- Hand-foot-mouth disease - statue of David with birds eating from hand food and mouth (rash)
- Aseptic meningitis - child shooting David with gun with a meningitis helmet on
- Herpangina - fever + ulcers on tonsils and palate (HFMD - HF)
What are the major viruses within the flavivirus family?
Yellow Fever virus, Dengue Fever virus, West Nile virus, Japanese Encephalitis, St. Louis Encephalitis, and Hepatitis C
Why is hepatitis C often given its own subdivision within the Flavivirus family?
All other flaviviruses use a 5’ cap for their +sense RNA
Hepatitis C is a “hepacivirus” - uses IRES-mediated translation similar to picornaviruses
What are the three major structural proteins of Flaviviruses?
- C protein - capsid
- E protein - envelope - major role in viral entry
- PrM protein - protease for maturation
Why has vaccination been unsuccessful for Flaviviruses and how does this work?
Antibody-dependent enhancement (especially dengue-virus)
Since flaviviruses mutate so quickly, previously protective antibodies bind but do not neutralize the new virions. These antibodies facilitate opsonization which allow viruses to more efficiently enter macrophages + enhance replication
How does RNA replication occur in flaviviruses vs picornaviruses?
Largely exactly the same, through a polyprotein intermediate, yielding 10 mature proteins in the cytoplasm
What are three major non-structural proteins of flaviviruses?
NS1: Soluble hemagglutin, eliciting a humoral immune response
NS3: Viral protease
NS5: RNA dependent RNA polymerase
What are the reservoir and vector of West Nile Virus and who does it infect? How can it be controlled?
Reservoir: Birds
Vector: Culex mosquito
Infects: Humans and horses, especially in summer months
Controlled via Ribavirin and mosquito control
What are the symptoms of West Nile?
Flu-like symptoms, with high fever, malaise, rash, myalgia, and lymphadenopathy
Often leads to aseptic meningitis or encephalitis, seizures and coma per sketchy
What is the vector for Yellow fever and when in history has it caused problems?
Aedes Aegypti mosquito, devastated US army in Cuba during Spanish-American war + during Panama Canal construction
What are the symptoms of Yellow fever?
Bloody diarrhea, vomiting, jaundice, high fever, backache from renal failure, and headache
Is there a vaccine for yellow fever and dengue virus?
Yellow fever - yes, live, attenuated
Dengue - No, due to antibody-dependent enhancement
What are the relevant serotypes of Dengue fever?
2 - America - associated with “breakbone fever” bone broken into two pieces on sketchy
1 and 3 - Central / South America
What are the diseases associated with Dengue virus? What transmits it?
- Dengue hemorrhagic fever (DHF) - remember breakbone fever and hemorrhaging / renal failure
- Dengue shock syndrome (DSS)
Transmitted by mosquitos
What is the leading cause of epidemic flavivirus encephalitis in the US and what transmits it?
St. Louis encephalitis - transmitted by mosquitos, elders at greatest risk for severe disease
How is Zika Virus transmitted?
- Through bite of infected Aedes mosquito (same as yellow fever)
- Sexual contact - only mode of transfer so far in U.S.
What are the symptoms of Zika?
Fever, rash, joint pain, and conjunctivitis
Why is Zika of major concern?
Mothers infected while pregnant could allow Zika Virus to cross placenta and attack fetal nerve cells, including some that develop in the brain
-> cause microcephaly
What is an Arbovirus?
Arthropod-borne virus -> any virus transmitted by mosquito or tic vector
What major viruses fall in the Togavirus family?
Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), Rubella virus and Chikungunya virus
What are the characteristics of the Togaviruses? What is the major difference from Flaviviruses?
Enveloped virus with ss +RNA
Togaviruses express structural proteins more towards the 3’ end, vs. Flaviviruses which express structural proteins more towards 5’ methylated cap.
What is the transmission of EEE similar to?
West Nile virus
Same reservoir, carrier, infections, symptoms, and transmission
What is the pathology of EEE?
Small hemorrhages in the brain and extensive neuronal damage - very severe and fatal disease if required (only 178 cases in 30 years)
What transmits Chikungunya virus and what is the saying associated with it?
Aedes mosquito - like Yellow Fever and Zika Virus
Characterized by fever, arthritis, and joint pain
“Bent out of shape” due to arthritis
What family is Rabies virus in and how is it transmitted?
Rhabdovirus,
It is a zoonotic infection transmitted by animal bite (infected saliva)
What are the characteristics of the rabies virus?
Bullet shaped virus, with -RNA genome, RNA-dependent RNA transcriptase.
Ribonucleoprotein - RNP = most infectious component of virus
Replicates in cytoplasm
What are the reservoirs of Rabies in developing and developed nations?
Developing: Primarily domestic animals (i.e. stray dogs)
Developed: Primarily wild animals (i.e. skunk, foxes, bats)
How long can Rabies incubation take and where does it travel?
Can take up to 12 months, enters through nerves / muscles and binds to nicotinic Ach receptors at the NMJ, then travels up to DRG and ultimately CNS. It is targeted towards CNS and submaxillary salivary glands (foaming at the mouth)
What are the early symptoms of Rabies?
Non-specific flu-like signs, increased muscle tone, and “hydrophobia” - fear of water
What are the late signs of Rabies?
Cerebral dysfunction with anxiety, confusion, agitation, abnormal behavior, “hypersalivation”, hallucinations, and insomnia
What can be seen in pathology of Rabies?
Cytoplasmic eosinophilic inclusion bodies called “Negri bodies” within neuronal cells
Especially pyramidal cells of hippocampus and purkinje cells
How is Rabies detected?
Fluorescent antibody assay or RT-PCR. Possibly histological examination for Negri bodies in autopsy
Is there a treatment for Rabies?
Not after symptoms appear
Pre-exposure prophylaxis for veterinarians and Zookeepers
Post-exposure vaccine for anyone possible exposed
What is recommended for postexposure treatment of Rabies?
- Local wound treatment - soap and water on the wound
- Passive immunization via human rabies immunoglobulins from Rabies-immunized people
- Human diploid cell vaccine (HDCV) - vaccine containing inactivated virus
How is rabies prevented in a public health sense?
Vaccinate wild and domestic animals so they can’t get it.
