2 - Viral Lifecycles 1: Lytic Replication Flashcards

1
Q

How fast can viruses replicate within cells?

A

After initial infection in cell, there is an eclipse period while macromolecular synthesis occurs, then a burst size in which progeny are released from the cell via lysis.

In less than 8 hours, some viruses have gotten to 100,000 particles/cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the outcome of infections caused by lytic replication?

A

Productive infection - generally leads to cytopathic effect with a burst of virus production

Causes an acute infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Most RNA viruses are _____.

A

Lytic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the diseases associated with Picornaviruses and what illness each is associated with?

A
  1. Enteroviruses: paralysis (polio and non-polio), common cold, meningitis, diarrhea, hand-foot-mouth disease
  2. Rhinoviruses: common cold
  3. Hepatoviruses: hepatitis
  4. Parechovirus: gastroenteritis, myocarditis, encephalitis.
  5. Kobuvirus: gastroenteritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What factors contribute to Picornaviruses pathogenesis and disease?

A

Cellular receptors
Permissiveness of the cell
Induced cell/host factors: cytokine and immune response
Speed of virus replication
Spread of infection between tissues and organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the picornavirus cellular receptors?

A
Coxsackie: Car 
Poliovirus: Pvr
Rhinovirus: Icam-1
Echovirus: CD55
Hepatitis A: HAVcr-1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the infection and disease associated with polio virus?

A

Inapparent (subclinical) infections (90-95%) - virus recovered from throat or stool, asymptomatic.

Mild illness (4-8%): minor undifferentiated febrile illness with occasional URI or gastroenteritis

Aseptic meningitis (non-paralytic polio) (1-2%): minor illness progresses to CNS invasion, stiffness in neck/back, disease 2-10 days. Rapid and complete.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are characteristics of paralytic poliomyelitis?

A

Initial non-specific febrile illness. Asymmetric flaccid paralysis, lower extremities involved more than upper, larger muscle groups involved more.

Bulbar paralysis from CN involvement, medulla, and respiratory compromise.

Recovery slow: 2 years for 100%. Can cause residual paralysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the stages in the progression of poliovirus infection?

A

Digestive stage in pharynx and small intestine, shed in feces.

Lymphatic stage in cervical and mesenteric lymph nodes.

Viremia: virus in blood and extraneural tissues - crosses BBB

Neural stage: Virus enters CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the sites of poliovirus infection in the order they occur? What other enteroviruses can do this?

A
  1. Oral ingestion
  2. Alimentary tract
  3. Blood
  4. (crosses BBB) Central nervous system
  5. Skeletal muscle

All other enteroviruses can do this, they just don’t do it as often as poliovirus does.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the ways to diagnose picornavirus?

A

Virus isolation from stool, rectal swab, throat swab, or CSF. Specific, sensitive, time consuming. See the cytopathic effects (lysis).

Serologic: look for increased antibody response to virus

PCR (multiplex) most common, fast and very specific.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the epidemiology of polio? How and when is it spread?

A

Poliomyelitis is a human disease only.

Fecal-oral transmission enhanced by persons with subclinical infections who shed virus in stool.

Summer epidemics in temperate climates (true for many other enteroviruses).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the three major epidemiological phases of polio?

A
  1. Endemic: children encounter at early age, maternal Ab protects then. High rate of subclinical infection, low paralytic disease.
  2. Epidemic: 1800-1900s US. Advent of indoor plumbing. Patients are older when first encounter virus and have higher incidence of paralytic disease.
  3. Post-vaccine: small # of cases, most all cases are vaccine related (from reverting attenuated virus).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What type of virus is picornavirus? What pH are they stable at?

A

ssRNA (+)

Enteroviruses stabel at pH 3-9
Rhinovirus: unstable below pH 6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the size and structure of picornavirus?

A

22-30 nm, Icosahedral, with NO lipid envelope and NO tegument.

Four structural proteins: VP1-4.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the first three steps in picornavirus replication?

A
  1. interaction of virus with receptors on cell surface weakens capsid

2.genome injected through virion across cell membrane
2’. Alternatively virion is endocytosed and genome released

  1. Genome used as mRNA for protein synthesis
17
Q

What are the last three steps in picornavirus replication?

A
  1. Polyprotein is proteolytically cleaved into individual proteins, including RdRp
  2. Macromolecular synthesis proceeds in a vesicle. Polymerase makes a - strand template from the genome and replicates the genome VPg is covalently attached to 5’ end.
  3. Structural proteins associate into the capsid structure, genome is inserted, and virions are released on cell lysis.
18
Q

How does a picornavirus enter into a cell and release its genome?

A

It binds via specific cell receptors and is brought in by endocytosis.

Viral particle interaction with cell receptor causes a 3D change that makes pore to let viral RNA into the cell

19
Q

What is the structure of the picornavirus genome?

A

It has a VPg at the 5’ end, an IRES region where the host ribosome binds, structural genes (VP1-4), and non-structural region that makes 2A, 3C, and RdRp

20
Q

What are the function of 2A, 3C, and RdRp genes in the picornavirus genome?

A

2A Set up factory inside the cell that collects everything together for repackaging

3C protease (3C does majority of cleaving of polyprotein)

RdRP: RNA dependent RNA Pol

21
Q

What is the function of having VPg at the 5’ end of the picornavirus?

A

Important for packaging into progeny and replication with RNA dependent RNA polymerase (RdRp).

22
Q

What is the effect of proteolytic processing on the host cell?

A

Inhibition of translation that plays a role in cell death.

23
Q

What are ways to prevent and control picornavirus?

A

Block attachment of virus by blocking receptors with antibodies or chemicals.

Block entry and genome release.

Protease processing

RdRp inhibitors

24
Q

What is the function of WIN 52035-2?

A

It blocks the groove on the virus so the viral particle is more stable and can’t uncoat and release it’s genome in the host.

25
Q

What is the best option for prevention and control of picornavirus?

A

An antibody in the binding site of the virus prevents viral attachment to a host cell.

This is how the polio vaccine works.

26
Q

What are the different polio vaccines and when were they initiated?

A

Inactivated vaccine in 1955 saw huge drop in polio cases.

Oral vaccine in 1962 caused an even further drop in polio.

27
Q

What are two examples of simple lytic enveloped RNA viruses?

A

Togavirus and flavivirus

28
Q

How does the replication of togavirus differ from that of picornavirus?

A

Togavirus is + strand but with envelope so it has to get a merger of virus envelope with cell membrane

Togavirus makes full length + stranded RNA and also subgenomic mRNAs used to translate into capsule proteins

Togavirus needs proteins in different amts: needs a lot of capsule proteins to encapsulate virus, but doesn’t need as many RNA dependent RNA Pol, so to be energy efficient it needs to make more capsule prpoteins than RDRP

29
Q

Describe the genomes of negative strand RNA viruses? What are examples?

A

Can be non-segmented or segmented genomes, with each segment transcribed separately.

Bunyaviruses
Filoviruses 
Orthomyxoviruses
Paramyxoviruses
Rhabdoviruses
30
Q

Describe the genomes of double stranded RNA viruses? What is an example of one?

A

Segmented genomes, with each segment transcribed separately to produce monocistronic mRNAs.

Reoviruses

31
Q

What are structural characteristics of the adenovirus? What is its genome and structure?

A

dsDNA genome
Not enveloped
Icosahedral capsid has penton spikes with fiber attachment proteins

Particle is much more complicated machine than picornavirus particle.

32
Q

Describe the replication of adenovirus?

A
  1. receptor and AV integrin coreceptor associate with penton base and fiber on virus.
  2. Virus endocytosed, acidified breaks down
  3. Proteins on virus are nuclear localization proteins
  4. Early genes transcribed, replication occurs, late phase occurs (which is primarily structural proteins)
  5. Transport of RNA into cytoplasm for translation
  6. Viral assembly and release of virus by cell lysis.
33
Q

Describe the temporal control of viral replication with adenovirus?

A

Early proteins E1A and E1B put the cell into S phase to replicate

Late proteins are structural

Virus uses splicing to maximize coding capacity.

34
Q

What signifies whether a protein is early or late in the adenovirus replication process?

A

In general early proteins are made before DNA replication and late proteins are make after DNA replication.

35
Q

What is used extensively by adenoviruses and was first discovered in adenoviruses?

A

SPLICING.

Multiply spliced mRNA and alternative splicing are used to make a variety of polypeptides from each promoter.

36
Q

What is the epidemiology of adenovirus? How is it spread?

A

> 50 serotypes infect humans, wide disease spectrum.Spread fecal/oral for some, respiratory for others.

Freq cause unapparent respiratory infections - latency

Original isolate from normal adenoid tissues: latent virus in adenoids and tonsils

37
Q

How can we prevent adenovirus?

A

Live attenuated adenovirus vaccine available and is routinely given upon entry into the armed forces.

Previous vaccine was discontinued in 1999, but the new vaccine is essentially the same formulation.