Viral CNS infections

Question 1

What are the three types of virus within the picornavirus family?

Answer 1

1. Enterovirus - i.e. poliovirus / coxsackievirus
2. Rhinovirus
3. Hepatovirus - i.e. Hep A

Question 2

What is the primary structural difference between Entervirus/Hepatovirus and Rhinovirus?

Answer 2

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

Question 3

What is the present in the 5’ UTR (untranslated region) of picornaviruses?

Answer 3

“Clover leaf” called Internal Ribosome Entry Site (IRES) which takes the place of the 5’ cap of RNA and controls translation

Question 4

What is the VPg protein?

Answer 4

Protein linking to the 5’ end of viral RNA of picornaviruses, provides the polyU primer for RNA synthesis

Question 5

What is the function of the 3’-UTR in picornaviruses

Answer 5

Controls RNA synthesis

Question 6

What are P1-P3 and what is their general function?

Answer 6

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

Question 7

What receptor do picornaviruses use, and specifically what receptor does polio use?

Answer 7

Wide variety of host cell surface receptors

Polioviruses use a single Pvr (polio virus receptor)

Question 8

Where do picornaviruses replicate?

Answer 8

In the cytoplasm

Question 9

What is the mechanism of RNA replication in picornaviruses?

Answer 9

Use +RNA genome to make -RNA strand from which multiple +RNA’s are made (via RNA-dependent RNA polymerase)

Question 10

What protein encodes the RNA-dependent RNA polymerase in picornaviruses?

Answer 10

3D

Question 11

What must the 3D protein work in conjunction with to function?

Answer 11

VPg - which provides the polyU primer for RNA synthesis

Question 12

What three loci encode viral proteases?

Answer 12

L, 2A, and 3C

Question 13

Where does poliovirus try to replicate?

Answer 13

The lymphoid tissue of oropharynx and gut - i.e. tonsils, cervical nodes, Peyer’s patches, mesenteric nodes

Question 14

What is the difference between transient and major viremia?

Answer 14

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

Question 15

What part of the CNS does polioviral replication occur? What can this lead to?

Answer 15

Mainly gray matter, especially the motor neurons in the anterior horn of the spinal corn. In severe cases, this can lead to flaccid paralysis

Question 16

Where does poliovirus get excreted?

Answer 16

In the feces

Question 17

What are the two types of poliovirus vaccines and which one is more effective in elliciting a long-term response?

Answer 17

1. Salk - inactivated - given intramuscularly

2. Sabin - live, attenuated - given orally and most protective / longest term response

Question 18

Why is eradication of polio very possible?

Answer 18

Humans are the only reservoir, vaccine is stable and easy to transfer with long-lasting immunity

Question 19

What are three conditions caused by Cocksackie A virus?

Answer 19

1. Hand-foot-mouth disease - statue of David with birds eating from hand food and mouth (rash)
2. Aseptic meningitis - child shooting David with gun with a meningitis helmet on
3. Herpangina - fever + ulcers on tonsils and palate (HFMD - HF)

Question 20

What are the major viruses within the flavivirus family?

Answer 20

Yellow Fever virus, Dengue Fever virus, West Nile virus, Japanese Encephalitis, St. Louis Encephalitis, and Hepatitis C

Question 21

Why is hepatitis C often given its own subdivision within the Flavivirus family?

Answer 21

All other flaviviruses use a 5’ cap for their +sense RNA

Hepatitis C is a “hepacivirus” - uses IRES-mediated translation similar to picornaviruses

Question 22

What are the three major structural proteins of Flaviviruses?

Answer 22

1. C protein - capsid
2. E protein - envelope - major role in viral entry
3. PrM protein - protease for maturation

Question 23

Why has vaccination been unsuccessful for Flaviviruses and how does this work?

Answer 23

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

Question 24

How does RNA replication occur in flaviviruses vs picornaviruses?

Answer 24

Largely exactly the same, through a polyprotein intermediate, yielding 10 mature proteins in the cytoplasm

Question 25

What are three major non-structural proteins of flaviviruses?

Answer 25

NS1: Soluble hemagglutin, eliciting a humoral immune response NS3: Viral protease NS5: RNA dependent RNA polymerase

Question 26

What are the reservoir and vector of West Nile Virus and who does it infect? How can it be controlled?

Answer 26

Reservoir: Birds Vector: Culex mosquito Infects: Humans and horses, especially in summer months Controlled via Ribavirin and mosquito control

Question 27

What are the symptoms of West Nile?

Answer 27

Flu-like symptoms, with high fever, malaise, rash, myalgia, and lymphadenopathy Often leads to aseptic meningitis or encephalitis, seizures and coma per sketchy

Question 28

What is the vector for Yellow fever and when in history has it caused problems?

Answer 28

Aedes Aegypti mosquito, devastated US army in Cuba during Spanish-American war + during Panama Canal construction

Question 29

What are the symptoms of Yellow fever?

Answer 29

Bloody diarrhea, vomiting, jaundice, high fever, backache from renal failure, and headache

Question 30

Is there a vaccine for yellow fever and dengue virus?

Answer 30

Yellow fever - yes, live, attenuated Dengue - No, due to antibody-dependent enhancement

Question 31

What are the relevant serotypes of Dengue fever?

Answer 31

2 - America - associated with "breakbone fever" bone broken into two pieces on sketchy 1 and 3 - Central / South America

Question 32

What are the diseases associated with Dengue virus? What transmits it?

Answer 32

1. Dengue hemorrhagic fever (DHF) - remember breakbone fever and hemorrhaging / renal failure 2. Dengue shock syndrome (DSS) Transmitted by mosquitos

Question 33

What is the leading cause of epidemic flavivirus encephalitis in the US and what transmits it?

Answer 33

St. Louis encephalitis - transmitted by mosquitos, elders at greatest risk for severe disease

Question 34

How is Zika Virus transmitted?

Answer 34

1. Through bite of infected Aedes mosquito (same as yellow fever) 2. Sexual contact - only mode of transfer so far in U.S.

Question 35

What are the symptoms of Zika?

Answer 35

Fever, rash, joint pain, and conjunctivitis

Question 36

Why is Zika of major concern?

Answer 36

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

Question 37

What is an Arbovirus?

Answer 37

Arthropod-borne virus -> any virus transmitted by mosquito or tic vector

Question 38

What major viruses fall in the Togavirus family?

Answer 38

Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), Rubella virus and Chikungunya virus

Question 39

What are the characteristics of the Togaviruses? What is the major difference from Flaviviruses?

Answer 39

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.

Question 40

What is the transmission of EEE similar to?

Answer 40

West Nile virus | Same reservoir, carrier, infections, symptoms, and transmission

Question 41

What is the pathology of EEE?

Answer 41

Small hemorrhages in the brain and extensive neuronal damage - very severe and fatal disease if required (only 178 cases in 30 years)

Question 42

What transmits Chikungunya virus and what is the saying associated with it?

Answer 42

Aedes mosquito - like Yellow Fever and Zika Virus Characterized by fever, arthritis, and joint pain "Bent out of shape" due to arthritis

Question 43

What family is Rabies virus in and how is it transmitted?

Answer 43

Rhabdovirus, It is a zoonotic infection transmitted by animal bite (infected saliva)

Question 44

What are the characteristics of the rabies virus?

Answer 44

Bullet shaped virus, with -RNA genome, RNA-dependent RNA transcriptase. Ribonucleoprotein - RNP = most infectious component of virus Replicates in cytoplasm

Question 45

What are the reservoirs of Rabies in developing and developed nations?

Answer 45

Developing: Primarily domestic animals (i.e. stray dogs) Developed: Primarily wild animals (i.e. skunk, foxes, bats)

Question 46

How long can Rabies incubation take and where does it travel?

Answer 46

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)

Question 47

What are the early symptoms of Rabies?

Answer 47

Non-specific flu-like signs, increased muscle tone, and "hydrophobia" - fear of water

Question 48

What are the late signs of Rabies?

Answer 48

Cerebral dysfunction with anxiety, confusion, agitation, abnormal behavior, "hypersalivation", hallucinations, and insomnia

Question 49

What can be seen in pathology of Rabies?

Answer 49

Cytoplasmic eosinophilic inclusion bodies called "Negri bodies" within neuronal cells Especially pyramidal cells of hippocampus and purkinje cells

Question 50

How is Rabies detected?

Answer 50

Fluorescent antibody assay or RT-PCR. Possibly histological examination for Negri bodies in autopsy

Question 51

Is there a treatment for Rabies?

Answer 51

Not after symptoms appear Pre-exposure prophylaxis for veterinarians and Zookeepers Post-exposure vaccine for anyone possible exposed

Question 52

What is recommended for postexposure treatment of Rabies?

Answer 52

1. Local wound treatment - soap and water on the wound 2. Passive immunization via human rabies immunoglobulins from Rabies-immunized people 3. Human diploid cell vaccine (HDCV) - vaccine containing inactivated virus

Question 53

How is rabies prevented in a public health sense?

Answer 53

Vaccinate wild and domestic animals so they can't get it.