Iahi: 3.1 - Lifestyles Of Lytic Viruses

Front 1

What are the physical properties of a Picornavirus?
- Size
- Morphology / Shape
- Nucleic Acid / Polarity
- Other features

Back 1

- 22-30 nm (very small)
- Icosahedral
- ssRNA + polarity
- No lipid envelope
- No tegument

Front 2

What are some types of Picornaviruses?

Back 2

- Enteroviruses
- Rhinoviruses
- Hepatoviruses

Front 3

What is the pH stability of the picornaviruses: enterovirus and rhinovirus?

Back 3

- Enterovirus - stable at pH 3-9
- Rhinovirus - unstable below pH 6

Front 4

What do enteroviruses cause? What kind are they?

Back 4

- Paralysis (non-polio and polio-type), common cold, meningitis, diarrhea
- Picornavirus

Front 5

What do rhinoviruses cause? What kind are they?

Back 5

- Common cold
- Picornavirus

Front 6

What do hepatoviruses cause? What kind are they?

Back 6

- Hepatitis
- Picornavirus

Front 7

How are enteroviruses spread?

Back 7

* Human fecal matter *
- Via hands
- Via sewage --> water supply
- Via solid waste landfills --> water supply
- Water supply directly or via shellfish

Front 8

Why are enteroviruses transmittable by fecal-oral route, fomites, or on hands?

Back 8

Capsid structure is resistant to mild sewage treatment, salt water, detergents, and temperature changes

Front 9

What are the characteristics of Picornavirus cellular receptors?

Back 9

- Wide variety
- Different families can use same/similar receptors
- Within a family can use different receptors

Front 10

What are the possible outcomes of a polio infection? Percentages?

Back 10

- Inapparent (subclinical) infection - 90-95%
- Mild (minor) illness - 4-8%
- Aseptic meningitis (nonparalytic polio) - 1-2%
- Paralytic Poliomyelitis - 0.1-2%

Front 11

What are the characteristics of an inapparent (subclinical) polio infection?
- Frequency
- Symptoms

Back 11

- 90-95% of cases
- Virus recovered from throat and/or stool
- Patient is asymptomatic

Front 12

What are the characteristics of a mild (minor) illness from polio?
- Frequency
- Symptoms

Back 12

- 4-8% of cases
- Minor undifferentiated febrile illness
- Occasional upper respiratory infection
- Influenza-like illness; gastroenteritis

Front 13

What are the characteristics of an aseptic meningitis from polio?
- Frequency
- Symptoms
- Recovery

Back 13

- 1-2% of cases
- Non-paralytic
- Minor illness progresses to CNS invasion
- Stiffness and pain in back and neck
- Disease lasts 2-10 days; rapid and complete recovery

Front 14

What are the characteristics of a paralytic poliomyelitis?
- Frequency
- Symptoms
- Recovery

Back 14

- 0.1-2%
- Initial non-specific febrile illness
- Spectrum of paralytic disease is variable (only isolated muscle groups or extensive paralysis)
- Asymmetric flaccid paralysis, lower extremities more than upper, large muscle groups involved more often
- Bulbar paralysis - CN, medulla, respiratory compromise, death 5% overall
- Slow recovery (2 years for 100%)
- Complications: residual paralysis

Front 15

What is the progression of Poliovirus?

Back 15

- Virus in oropharynx (days 0-3)
- Minor illness (fever, malaise, headache, nausea) and viremia (gets into blood) (days 3-6)
- Antibodies formed ~ day 5
- CNS invasion / major illness - meningitis ~ day 6
- Virus in stool ~ day 6
- Paralysis ~ day 8

Front 16

How do you diagnose Picornavirus?

Back 16

- Virus isolation from stool specimens and throat washings, or CSF (specific, sensitive, but time consuming to do a cell culture)
- Serologic - neutralization - type specific (look for ≥4x rise in titer - acute vs. convalescent)
- PCR (multiplex) - rapid and specific

Front 17

Poliomyelitis can affect what hosts?

Back 17

Exclusively humans

Front 18

How is poliovirus spread between people? When/where is it spread more commonly?

Back 18

- Fecal-oral route
- Enhanced by persons with sub-clinical infections
- Summer epidemics in temperate climates (true for many other enterovirus diseases)

Front 19

What are the three major epidemiological phases of poliovirus?

Back 19

- Endemic
- Epidemic
- Post-vaccine

Front 20

What are the characteristics of the "Endemic" phase of polio?

Back 20

- Children encounter virus at an early age
- Maternal antibody offers protection
- High rate of subclinical infections
- Very low incidence of paralytic disease

Front 21

What are the characteristics of the "Epidemic" phase of polio?

Back 21

- Late 1800s and early 1900s in US
- Coincides with advent of indoor plumbing
- Patients are older when they first encounter virus
- Higher incidence of paralytic disease in older children and adults

Front 22

What are the characteristics of the "Post-Vaccine" phase of polio?

Back 22

- Small number of cases
- Most all cases are vaccine related

Front 23

What caused the transition of Polio from an "Endemic" disease to an "Epidemic" disease?

Back 23

- Endemic - children would encounter the poliovirus at an early age when they were still protected by maternal antibodies (low incidence of paralytic disease)
- Epidemic - during late 1800s/early 1900s the advent of indoor plumbing led to people encountering the poliovirus at an older age (increased incidence of paralytic disease because no longer protected by maternal antibodies)

Front 24

What steps happen in a poliovirus infection?

Back 24

1. Receptor binding and entry into host cell
2. Uncoating of virus
3. Genome released into cytosol
4. Cap-free translation
5. Single polyprotein is self-cleaved to limit products (capsid and non-structural proteins)
6. RNA-dependent RNA replication on vesicles (this machinery provided by virus)
7. Encapsidation of RNA into capsid proteins
8. Viral exit

Front 25

How does poliovirus enter the host cell and release its genome (steps 1-3)

Back 25

- Interactions of host cell and virus via ICAM-1 binding in "canyon area"
- Leads to endocytosis
- Injection mechanism of RNA into cytoplasm through membrane

Front 26

How does poliovirus translate and cleave its polyprotein (steps 4-5)?

Back 26

- Host machinery translates a single polypeptide
- Proteases cut up the polyprotein with enzymes encoded on the polyprotein
- Inhibits host cell translation and plays a role in cell death

Front 27

What kind of genome do picornaviruses have? Effect on replication / transcription / translation?

Back 27

- +sense ssRNA (can't be a template for making + mRNA
- Copied to make a -sense ssRNA (acts as template to make more +sense RNA which can be translated into protein)
- Temporarily forms dsRNA which indicates there is an invader (dsRNA is not found normally in a human) --> sets off immune system

Front 28

What important protein is released from the polyprotein that poliovirus encodes?

Back 28

An RNA-dependent RNA polymerase (not provided by host cell) - makes a (-) strand template from the genome and replicates the genome, such that a + mRNA can be created for continued translation

Front 29

What prevention and control treatments are available for Picornaviruses?

Back 29

- Block receptors used for viral attachment (antibodies or chemicals)
- Virus entry and genome release --> Pleconaril
- Protease processing --> Ruprintrivir
- RNA-dependent RNA polymerase inhibitors --> Ribavirin

Front 30

Which drug is used to prevent picornavirus entry and genome release?

Back 30

Pleconaril

Front 31

Which drug is used to prevent protease processing of picornavirus?

Back 31

Ruprintrivir

Front 32

Which drug is used to inhibit RNA-dependent RNA polymerase from picornavirus?

Back 32

Ribavirin

Front 33

What vaccines were created for Poliovirus? Success?

Back 33

- 1955 - inactivated virus vaccine (Salk)
- 1962 - live attenuated virus vaccine (Sabin)
Now: <1 case / 100,000 people

Front 34

Now, what causes paralytic poliomyelitis cases?

Back 34

Now essentially all are vaccine-associated

Front 35

What is the difference between segmented and non-segmented genomes?

Back 35

- Segmented genomes have each segment transcribed separately to produce monocistronic mRNAs
- Non-segmented genomes translate a polyprotein that is cleaved to produce separate proteins

Front 36

Where can adenovirus be isolated from?

Back 36

Normal adenoid tissues - latent virus in adenoids and tonsils

Front 37

How many serotypes of adenovirus are there? How do they differ in terms of disease?

Back 37

- 51 serotypes
- Each associated with different disease spectrum
- Cross-reactivity - family common antigen reduces infection with other types and re-infection is rare
- Frequently causes unapparent respiratory infections (latency)

Front 38

What is the genome and structure of adenoviruses?

Back 38

- dsDNA
- Icosahedral capsid with penton spikes
- Not enveloped

Front 39

How does the structure of the adenovirus particle compare to the picornavirus particle?

Back 39

Adenovirus particle is much more complicated

Front 40

What kind of diseases can be caused by Adenoviruses?

Back 40

- Gastrointestinal Ad40 and 41 in children
- Respiratory
- Hepatitis
- Genitourinary
- Ocular
- Encephalitis
- Systemic
- More severe in immunosuppressed, especially pneumonia and gastrointestinal disease

Front 41

What ist he timeline for an enteric adenovirus infection?

Back 41

- Incubation 3-10 days
- Diarrhea lasts 6-9 days
- May have vomiting and fever preceding diarrhea

Front 42

What kind of people are more commonly affected by Adenoviruses?

Back 42

More common in children than adults, causes 5-15% of gastroenteritis in young children

Front 43

How does the tropism of adenovirus compare to picornavirus?

Back 43

Similar tropism - but radically different virus

Front 44

How does adenovirus mediate attachment and entry into host cells?

Back 44

- Viral surfing (DAF interaction)
- Clathrin mediated endocytosis of naked viruses
- Viral fusion pore control (some envelopes of virus fuse with membrane)

Front 45

How do adenoviruses affect epithelial cells?

Back 45

- Virus attaches to apical surface and enters cell
- Virus released from basal surface
- Excess virus penton spike fibers released from cells disrupts adhesion junctions (CAMs)
- Virus sheds into intestinal lumen via apical surface

Front 46

When an adenovirus enters the host cell what happens to it?

Back 46

1. Loses penton spikes
2. Loses penton / envelope
3. Enters Nucleus and DNA is released

Front 47

How do adenoviruses generate diversity?

Back 47

Removal of introns by RNA processing

Front 48

What was discovered during the study of Adenoviruses?

Back 48

Splicing - multiply spliced mRNAs and alternative splicing - used to make a variety of polypeptides from each promotor

Front 49

How long does it take for Adenovirus entry into host cells to lysis and release?

Back 49

18-20 hours

Front 50

When are Adenovirus vaccines utilized?

Back 50

In the military because it commonly spreads in the barracks