Lecture on Picornaviridae, Togaviridae, and Flaviviridae Viruses

Picornaviridae, Togaviridae, and Flaviviridae Overview

Lecture 14: Picornaviridae Togaviridae Flaviviridae

Lecture Objectives

• LO1: Describe the structural features of Picornaviridae
• LO2: Describe the clinical presentation of diseases caused by this viral family and prevention methods if such exist
• LO3: Describe the structural features of Toga and Flavivirade
• LO4: Describe clinical features of encephalitis, dengue fever (explain why second time is worse) and yellow fever
• LO5: Differentiate rubella from other childhood rashes
• LO6: Describe Hepatitis C and differentiate it from Hepatitis A and Hepatitis B

RNA Viruses: Genome and Infectivity

RNA viruses that do NOT have DNA phase

	IN VIRION	All code for RNA d. RNA pol	Plus-stranded RNA	No	Infectious	Translation
Genome	RNA-dependent RNA polymerase
Infectivity of RNA			Negative- stranded RNA	Yes	Non-infectious	Viral mRNA synthesis
Initial event in cell			Double- stranded RNA	Yes	Non-infectious	Viral mRNA synthesis

Polling Question: RNA-Dependent RNA Polymerase

Polling question: Which family of viruses encodes and carries an RNA dependent RNA polymerase? A. Togaviridae B. Arenaviridae C. Parvoviridae D. Picornaviridae E. Poxviridae

Diseases Caused by Viral Families

Picornaviridae Diseases

• Polio
• Herpangina
• Pleurodynia
• Myo/Pericarditis
• HFMD
• Meningitis
• Conjunctivitis
• Common cold
• Hepatitis A
• Coxsackie

Togaviridae Diseases

• WEE
• EEE
• VEE
• Rubella
• Chikungunya

Flaviviridae Diseases

• WNE
• JE
• Dengue fever
• Yellow fever
• Hepatitis C
• Zika

Picornaviridae Structure

Picornaviridae VPg (5') RNA capsid @ Elsevier. Murray: Medical Microbiology 5e - www.studentconsult.com

Picornavirus Serotypes

Polio: serotypes 1, 2, 3 Coxsackie A: serotypes 1-22, 24 Coxsackie B: serotypes 1-6 Rhinovirus > 100 serotypes

• Hepatitis A: also called enterovirus 72 Echoviruses: serotypes 1-9, 11-27, 29-34 http://mol-biol4masters.masters.grkraj.org/html/Genetic_RNA4-Picorna_Virus.htm

Features of Picornavirus

Naked, icosahedral

+RNA Genome alone is infectious

Bind to receptors that are members of immunoglobulin superfamily (such as ICAM-1)

Replicate entirely in the cytoplasm

NUCLEUS

Viral, rather than immune patholo gy causes sympto ms

All Picorna are cytolytic, except Hepatitis A

Very resistant to environment, except Rhino (not resistant to low pH)

Rhino grow best at 33º Celsius and stays in respiratory tract

Spread by fecal- oral route, ingestion of contaminated food, contact with infected hands or fomites, and inhalation of infectious aerosol

Infection is often asymptomatic or mild

Eneterovirus is shed in feces for a long time

Antibody! controls infection, prevents viremia and reinfection

Bottom line: Picornaviruses are stable RNA viruses. Many can be transmitted by fecal-oral route. Rhinoviruses prefer cooler temp. and are destroyed by low pH.

Picornavirus Replication Cycle

Picornavirus replication Receptor binding Entry Polypeptide processing Nucleus Uncoating Negative strand synthesis 5' IRES-driven translation 5º Positive strand (genome) synthesis 5º / '3' 5 / '3' 5' 3 5% 13 - 5' 3 Assembly Viral ogross Cell lysis Bottom line: Picornaviruses have a typical +RNA viral replication cycle VirusJ. Lindsay Whitton et al; http://www.nature.com/

Lecture Objectives Revisited

• LO1: Describe the structural features of Picornaviridae
• LO2: Describe the clinical presentation of diseases caused by this viral family and prevention methods if such exist
• LO3: Describe the structural features of Toga and Flavivirade
• LO4: Describe clinical features of encephalitis, dengue fever (explain why second time is worse) and yellow fever
• LO5: Differentiate rubella from other childhood rashes
• LO6: Describe Hepatitis C and differentiate it from Hepatitis A and Hepatitis B

Transmission of Enteroviruses

Transmission of enteroviruses Human fecal matter Hand Sewage Solid waste landfills Water supply Shellfish @ Elsevier. Murray: Medical Microbiology 5e - www.student

Properties of Rhino- and Entero-viruses

Table 3 Properties of Rhino- and Entero-viruses

	Rhino viruses	Entero viruses
pH sensitivity	labile to acid pH	resistant to acid pH
Optimum growth temperature	33 degrees C (approx)	37 degrees C (approx)
Detergent sensitivity	Resistant	Resistant
Serotypes	>100	72
Transmission	aerosol	oro-fecal
Site of primary infection	upper respiratory tract	gut

Clinical Outcomes of Poliomyelitis

Clinical outcomes of poliomyelitis (gray matter (polio), spinal cord (myel), inflammation (itis): Poliovirus Infection (4 outcomes):

1. Asymptomatic Illness

• 90% of cases
• Limited to gut and oropharynx.

2. Abortive Polio (Minor Illness)

• 5% of polio cases
• 3-4 days after infection
• Nonspecific illness: headache, vomiting, fever, malaise, sore throat, coryza
• Lasts a few days

Antibody Paralysis Major illness (meningitis) Meningeal irritation Stiffness of neck or back Minor illness Prodrome Fever CNS invasion malaise headache nausea Virus in stool Virus in oropharynx Viremia 0 3 5 6 10 12 35 @ Elsevier. Murray: Medical Microbiology 5e - www.studentconsult.com

3. Non-paralytic Polio (Aseptic Meningitis)

• 1 - 2% of people with polio
• Virus progresses from GI to blood to CNS (meninges)
• Symptoms include back pain and muscle spasms in addition to minor illness
• Circulating viruses cross the blood - brain barrier by transcapillary diffusion

Progression of poliovirus infection. Antibody Paralysis Major illness (meningitis) Meningeal irritation Stiffness of neck or back Minor illness Prodrome Fever malaise headache CNS invasion nausea Virus in stool Virus in oropharynx Viremia 0 3 5 6 10 12 35 @ Elsevier. Murray: Medical Microbiology 5e - www.studentconsult.com

Spinal Cord and Meninges

SPINAL CORD: Gray matter White matter Posterior median surms Central cama. Anterior median fissure SPINAL MENINGES: Spinal nerve Pia mater (inner) Arachnoid mater (middle) Dura mater (outer) Subarachnoid space https://ranzcrpart1.fandom.com/

4. Paralytic Polio (Major Illness)

• 0.1 - 2% of cases
• Appears 3 - 4 days after minor illness has subsided
• Virus travels from blood to alpha motor neurons in anterior horn of spinal cord and to primary motor cortex of the brain

Antibody Paralysis Major illness (meningitis) Meningeal irritation Stiffness of neck or back Minor illness Prodrome Fever malaise CNS invasion headache nausea Virus in stool Virus in oropharynx Viremia 0 3 5 6 10 12 35 @ Elsevier. Murray: Medical Microbiology 5e - www.studentconsult.com

Polio Outcomes

a) Spinal Polio

grey matter motor neurons of the anterior horn

• The virus gains access to anterior horn cell (gray matter) containing cell bodies of alpha motor neurons
• aMN is damaged > no stimulation of the skeletal muscle controlling limb movement
• This result is muscle weakness and flaccid paralysis
• Other symptoms:
• Muscle pain
• Fasciculations
• Hyperesthesia (increased sensitivity to stimuli)
• Spasm of involved muscle
• Accentuated tendon reflexes
• Takes years for recovery
• Respiratory center not affected

b) Bulbar Polio

Pons Cerebellum Medulla Spinal cord

• polio attacks cranial and cervical nerves: Nerves affected:
• Cranial Nerves:
• Trigeminal nerve (V)
• Facial nerve (VII)
• Glossopharyngeal nerve (IX)
• Accessory nerve (XI)
• Muscle atrophy in the facial muscles, pharynx, vocal cords
• Cervical nerves
• C3, C4, C5
• Diaphragm paralysis
• Results in death in 75 % of patients

c) Postpolio Syndrome

Normal Acute polio Post-polio Normal Acute paliomyelitis Post-palla

Mechanism of Active Paralytic Polio

4. Mechanism of active paralytic polio Undamaged Neuron Dying Neuron Damaged Neuron (Will Survive) · Dying TAS TAS https://www.polionsw.org.au/ Muscle Cell B. ACTIVE POLIO Bottom line: Polio virus causes mild illness in most people but can progress to flaccid paralysis and respiratory paralysis

Polio Prevention: Vaccines

Prevention Salk (killed, injected) Sabine (live, oral)

Vaccine Advantages

	Salk (killed, injected)	Sabine (live, oral)
Advantages	Stable Lifelong immunity Easy to transport Induction of secretory Ab (mimics natural infection) Easy to store Promotes indirect immunization Safe in immunodeficient Easy to administer No risk of illness No need for boosters

Vaccine Disadvantages

	Salk (killed, injected)	Sabine (live, oral)
Disadvantages	Lack of secretory Ab Risk of vaccine-associated polio Booster needed for life-long immunity	Spread of vaccine to contacts without consent Higher comminity immunization levels needed Not safe for immunodeficient people

TIME THE WEEKLY NEWSMAGAZINE Mar 29, 1954 Salk POLIO FIGHTER SALK I thị the year http://content.time.com Sabine Bottom line: Two forms of vaccine exist: Live - used by most of the world and Killed - used in the US. Killed vaccine is safer but requires boosters. http://www.laskerfoundation.org/

Polio Eradication Efforts

Polio recently 1988 2014* Countries that have never eliminated polio Countries that have never eliminated polio Countries that have eliminated polio Countries that have eliminated polio *As of April 29, 2014

Polio Comeback Concerns

Viral Infections > Polio Polio could be making a comeback. Here's what you need to know By Jules Murtha | Medically reviewed by Kristen Fuller, MD | Published November 21, 2022 Key Takeaways TABLE OF CONTENTS Key takeaways Polio's unexpected return Symptoms, risk factors Get vaccinated Sources f in The New York State Department of Health identified the first confirmed case of polio in the US in nearly a decade in July 2022. The patient was unvaccinated. Patients most at risk of contracting poliovirus include those who live or travel in places where polio has yet to be eradicated (or places with poor sanitation), as well as children under 5 and pregnant women, according to research. Although a cure for paralytic polio does not yet exist, physicians can encourage patients to protect themselves against the virus by receiving an inactivated poliovirus vaccine. Once a disease that struck fear among American masses in the late 1940s, polio was nearly eradicated by 1979. According to a CDC re- port, the polio vaccine enabled Americans to avoid up to 35,000+ an- nual cases-a statistic that used to keep parents from allowing their kids to go outside.[1]

Polio Diagnosis

• Virus isolation
• Pharynx in the first few days
• Feces for as along as 30 days.
• The virus is rarely found in CSF
• RT-PCR to detect genome in specimen
• Serology (antibody detection)
• IF
• ELISA

The Iron Lung

The iron chamber http://www.youtube.com/watch?v=6LTvhIR-Vz4 http://www.msnbc.msn.com/id/24859306/IRON LUNGS: In the 1950s thousands of youngsters were placed in mechanical ventilators such as these because their respiratory muscles were paralyzed. Pressure changes inside the chamber forced the chest to expand and contract, allowing patients to breathe.