2 - Viral Lifecycles 1: Lytic Replication Flashcards
How fast can viruses replicate within cells?
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
What is the outcome of infections caused by lytic replication?
Productive infection - generally leads to cytopathic effect with a burst of virus production
Causes an acute infection
Most RNA viruses are _____.
Lytic.
What are the diseases associated with Picornaviruses and what illness each is associated with?
- Enteroviruses: paralysis (polio and non-polio), common cold, meningitis, diarrhea, hand-foot-mouth disease
- Rhinoviruses: common cold
- Hepatoviruses: hepatitis
- Parechovirus: gastroenteritis, myocarditis, encephalitis.
- Kobuvirus: gastroenteritis
What factors contribute to Picornaviruses pathogenesis and disease?
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
What are the picornavirus cellular receptors?
Coxsackie: Car Poliovirus: Pvr Rhinovirus: Icam-1 Echovirus: CD55 Hepatitis A: HAVcr-1
Describe the infection and disease associated with polio virus?
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.
What are characteristics of paralytic poliomyelitis?
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.
Describe the stages in the progression of poliovirus infection?
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
Describe the sites of poliovirus infection in the order they occur? What other enteroviruses can do this?
- Oral ingestion
- Alimentary tract
- Blood
- (crosses BBB) Central nervous system
- Skeletal muscle
All other enteroviruses can do this, they just don’t do it as often as poliovirus does.
What are the ways to diagnose picornavirus?
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.
What is the epidemiology of polio? How and when is it spread?
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).
What are the three major epidemiological phases of polio?
- Endemic: children encounter at early age, maternal Ab protects then. High rate of subclinical infection, low paralytic disease.
- Epidemic: 1800-1900s US. Advent of indoor plumbing. Patients are older when first encounter virus and have higher incidence of paralytic disease.
- Post-vaccine: small # of cases, most all cases are vaccine related (from reverting attenuated virus).
What type of virus is picornavirus? What pH are they stable at?
ssRNA (+)
Enteroviruses stabel at pH 3-9
Rhinovirus: unstable below pH 6
What is the size and structure of picornavirus?
22-30 nm, Icosahedral, with NO lipid envelope and NO tegument.
Four structural proteins: VP1-4.
What are the first three steps in picornavirus replication?
- 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
- Genome used as mRNA for protein synthesis
What are the last three steps in picornavirus replication?
- Polyprotein is proteolytically cleaved into individual proteins, including RdRp
- 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.
- Structural proteins associate into the capsid structure, genome is inserted, and virions are released on cell lysis.
How does a picornavirus enter into a cell and release its genome?
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
What is the structure of the picornavirus genome?
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
What are the function of 2A, 3C, and RdRp genes in the picornavirus genome?
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
What is the function of having VPg at the 5’ end of the picornavirus?
Important for packaging into progeny and replication with RNA dependent RNA polymerase (RdRp).
What is the effect of proteolytic processing on the host cell?
Inhibition of translation that plays a role in cell death.
What are ways to prevent and control picornavirus?
Block attachment of virus by blocking receptors with antibodies or chemicals.
Block entry and genome release.
Protease processing
RdRp inhibitors
What is the function of WIN 52035-2?
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.
