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Picornaviruses

Eligius Lyamuya MD, MMed, PhD, FTAAS, FCPath (ECSA)
Department of Microbiology and Immunology
Muhimbili University of Health and Allied Sciences

Learning Objectives
• Know the classification of Picornaviruses
• Understand the general characteristics of
Picornaviruses
• Know the pathogenesis of and diseases caused by
important genera of Picornaviridae
• Know the principles of detection of infection by
Picornaviruses
• Comprehend the available strategies for prevention and
control of infections caused by Picornaviruses

Classification
• Family: Picornaviridae
• Genera
‒ Enterovirus
‒ Rhinovirus
‒ Hepatovirus
‒ Parechovirus
‒ Aphthovirus
‒ Cardiovirus
• Largest and important family of viral pathogens

Medical importance
Genus Disease
Enterovirus • Poliovirus type member The 3 major types cause
• Coxsackie A/B virus paralysis.
• Enterovirus type 71
• swine vesicular disease
• porcine enteroviruses
Rhinovirus Respiratory tract infections Colds in humans (110
types) and pigs
Hepatovirus • Hepatitis A Contagious liver
• Avian encephalomyelitis infections
Apthovirus Foot and mouth disease Most destructive in Africa
Cardiovirus Encephalomyocarditis virus Heart and brain
inflammation
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in one piece and of positive sense . VP3.Structure and composition • Smallest (pico) RNA viruses (25-30 nm) • Non-enveloped • Icosahedral capsid • Coat consists of 4 proteins VP1.VP4 • ssRNA. VP2.

Electron Micrograph of Picornaviruses .

• Responsible for many important diseases in humans and animals. • Bind to cell specific surface receptors and this interaction is an important factor in determining host and tissue specificity of each virus. Properties • Among the smallest pathogens of vertebrates. .

• Nucleocapsids are assembled and released by lysis. • Synthesis of new viral (+) RNA is through a complementary (-) strand. . Replication • Rapid replication in the cytoplasm because infecting viral RNA is equal to mRNA • A precursor polyprotein is translated and processed by viral enzymes.

Enteroviruses .

6 serotypes • Echoviruses − 32 serotypes • New enteroviruses − 4 serotypes (#68-71) . 23 serotypes − Group B. Enteroviruses • Polioviruses − 3 serotypes • Coxsackieviruses − Group A.

myocarditis. pleurodynia.Pathogenesis of Enteroviruses • Spread by fecal-oral route • Grow initially in the GI mucosa • Most infections are sub-clinical • Life long immunity post infection • Can cause a variety of severe diseases:- – meningitis. diarrhea . pericarditis. myalgia. herpangina. hand- foot-and mouth disease. paralysis disease. colds. exanthems.

Pathogenesis of Enteroviruses .

. • Humans are the only susceptible hosts. almost 100% of the population in developing countries became infected before the age of 5. and 3) but no common antigen. • Distributed globally. • Immunization campaign has eradicated poliovirus in most regions of the world except in the Indian Subcontinent and Africa. Poliovirus • 3 serotypes of poliovirus (1. 2. • Before the availability of immunization. • Identical physical properties but only share 36-52% nucleotide homology.

.14 days. Pathogenesis • First described by Michael Underwood in 1789 • Incubation period is usually 7 . the virus may disseminate and involve the CNS. • Ingestion multiplication in the oropharyngeal and intestinal mucosa invasion of the lymphoid system (in particular the tonsils and the Peyer's patches of the ileum) entry into blood stream resulting in a transient viremia. • In a minority of cases.

pass through blood brain barrier 7. Virus shed in feces . Infect cervical and small intestine lymph nodes 3. Infects Peyer’s patches 6.0 4. Human Poliomyelitis 1. Not inactivated by pH 3. bulbar polio 10. Fecal/oral route of entry 2. Viremia. Virus infects epithelium of large intestine 5. Infects anterior horn cells of motor neurons in spinal cord causing flaccid paralysis 8 and 9 Infects brain causing tissue damage---affects breathing.

Clinical outcomes • Subclinical infection (90 . • Major illness (1 . – Non-paralytic poliomyelitis: aseptic meningitis – Paralytic poliomyelitis: • involvement of the anterior horn cells leads to flaccid paralysis • involvement of the medulla may lead to respiratory paralysis and death.95%): account for the vast majority of poliovirus infections.8%): diagnosis can only be made by the laboratory.2%): may present 2 . • Abortive infection (4 .3 days following the minor illness or without any preceding minor illness. – Progressive post-poliomyelitis muscle atrophy: • Can appear decades after polio infection. not caused by viral recrudescence .

Polio – a paralysing disease for life .

Laboratory diagnosis • Cell culture • No new diagnostic methods developed .

oral-oral transmission is possible • Communicability period is 7-10 days before onset • Virus present in stool for 3-6 weeks • Most frequent cause of epidemic polio is poliovirus type 1 • Most vaccine associated cases are due to type 2 or 3. • Transmission is fecal-oral. • The virus does not survive long (less than a month) in the environment outside the human body. • Circulating wild type 2 poliovirus has not been isolated in the world since October 1999 . Epidemiology • Reservoir is human but there is no long-term carrier state.

• Disease can be prevented through vaccination.live attenuated trivalent. Prevention and control -1 • No specific antiviral therapy is available. oral administration (OPV) • Targeted for Global Eradication. ‒ Salk . .inactivated. percutaneous inoculation (IPV) ‒ Sabin .

associated infections • Produces local Induces both systemic Requires cold storage to immunity through the (IgG) and local (IgA) maintain potency induction of an IgA immunity response as well as Prepared in human cells. around kidney cells 1 in 3 million doses Induces herd immunity . eliminating risk of another enterovirus is • Rarely causes contamination with latent infecting a cell paralytic viruses found in monkey poliomyelitis. Live-attenuated (Sabin) oral polio vaccine (OPV) Attributes Advantages Disadvantages • Consists of live Relatively inexpensive and Can mutate to virulent attenuated virus of all easily administered strains and cause vaccine- 3 serotypes. Effect may be blocked if systemic immunity.

Requires parenteral • Prevents paralytic administration poliomyelitis since viremia is essential for the pathogenesis of the disease. Inactivated (Salk) injectable polio vaccine (IPV) Attributes Advantages Disadvantages • Consists of formalin Cannot revert to Fails to elicit local (gut) inactivated virus of all virulence immunity 3 poliovirus Does not require cold Stringent control of serotypes. . storage to maintain production required to • Produces serum potency to ensure inactivation antibodies (IgG) only: does not induce local Four booster immunity (IgA) and immunizations required thus will not prevent to confer immunity local infection of the Expensive gut.

Global Polio Eradication Initiative-1 • May 1988. the 42nd World Health Assembly approved a general Plan of Action for Global Polio Eradication . – initiative should be pursued in ways that would strengthen Extended Programme of Immunization – largest public health initiative in history • 1989. the 41st World Health Assembly committed the WHO Member States to the global eradication of poliomyelitis by the year 2000.

– National immunization days (NIDs) targeting all children <5 years. . and – Mop-up immunization campaigns to interrupt final chains of transmission. Global Polio Eradication Initiative-2 • Eradication strategies:- – High. routine infant immunization coverage with at least three doses of oral polio vaccine (OPV) plus a dose at birth in polio-endemic countries. – Acute flaccid paralysis (AFP) surveillance and laboratory investigations.

Nigeria.) are still endemic for Polio . Global Polio Eradication Initiative-3 • Last case of wild poliovirus infection in Tanzania reported in 1996 • The Americas. Western Pacific Region of WHO and Europe have been certified free of polio. Pakistan. • Tanzania declared polio free in 2013 • 3 countries (Afghanistan.

Major Milestones • Wild Polio Virus interruption = end of 2014 • tOPV – bOPV Switch = 2015/2016 • Global Certification = end of 2018 • bOPV cessation = 2019 .

Coxsackie viruses • Two groups A and B • 29 serotypes • Newborn mice are highly susceptible .

resolve without complications • Usually A16 . Pathogenesis-1 • Neurologic ‒ An aseptic meningitis ‒ A7 and A9 most common causes ‒ Polio-like. 8. but paralysis is rare ‒ Full recovery • Skin and mucosa ‒ Herpangina (severe pharyngitis) • A2-A6. 10 most common ‒ Hand-foot-and-mouth disease • Blisters on tissues.

Pathogenesis-2 • Cardiovascular and muscular (Group B) ‒ Pleurodynia • Chest pains. 1-2 weeks • Self resolving ‒ Myocarditis • Inflammation of the heart • Can be fatal in newborns • Survivors can have permanent heart damage • Others ‒ Acute hemorrhagic conjunctivitis ‒ Respiratory infections (“colds”) ‒ GI infections ‒ Diabetes? .

Foot and mouth disease • Highly contagious disease of domestic and wild ruminants and pigs. • Systemic disease with high fever. vesicles on epithelial surfaces • Not usually fatal in adults but causes economic losses (trade implications) • Can be fatal in young animals - myocarditis .

Laboratory diagnosis • Virus isolation • Serology • PCR .

Epidemiology • Major problem in domesticated livestock • Highly contagious • Mortality can reach 70% – Immunity is short-lived – Some cattle can remain persistently- infected for months .

Prevention and control • In countries with endemic FMD – vaccination – vaccination and slaughter • FMD free countries – prevent introduction – in face of outbreak • test and slaughter • ring-vaccination and slaughter • ring-vaccination and slaughter only sick animals .

encephalitis) – Febrile illnesses – Common colds . Echovirus • Enteric Cytopathogenic Human Orphan virus – More than 30 serotypes – GI and cold-like infections • Causes enteric infections in humans • Diseases include – Severe disease (aseptic meningitis.

Laboratory diagnosis • Isolation in monkey kidney cells • Serology • Nucleic acid detection techniques .

Epidemiology • Similar to that of enteroviruses • Occur globally • Dissemination of different serotypes may occur in waves .

Prevention and control • Avoid contact with patients • Use of immune globulin for neonates • No vaccines available .

Rhinovirus .

hands. There is no fever. . door handles. air. Rhinovirus pathogenesis • Transmission is by contact with respiratory secretions (e. inanimate objects) • Localized infections of the nose • Responsible for most cases of the common cold • More heat and acid labile than the enteroviruses • Symptoms occur 2 to 4 days after exposure and last about one week.g.

Rhinovirus Diseases • Most frequent cause of the common cold • In contrast to the other picornaviruses. the rhinoviruses produce localized infections • Each serotype (>115) is distinct – not cross-reactive – little cross-protection .

self-limiting • No effective vaccine . Epidemiology. prevention and control • Globally distributed • Transmission is by contact with respiratory secretions • No effective treatment.

Hepatovirus .

Hepatitis A Virus • Originally designated as enterovirus 72 • Now the only member of a separate genus • Causes an acute hepatitis syndrome .

• Very little complementary (minus sense) RNA is detectable in infected cell. Hepatitis A Viral Replication • Uncoating of virion is inefficient. • There is little cytopathic effect • Infection is non-cytocidal and persistent. • Cellular protein synthesis is not inhibited. .

Hepatitis A pathogenesis • Enters body by ingestion. • Lifelong immunity. • Virus detectable in feces and in low titers in blood and saliva 1-2 weeks prior to appearance of dark urine and disappears after serum transaminase levels reach their peak. . second attacks do not occur. no long-term sequelae. • Incubation period is about 4 weeks • Abrupt onset. multiplies in intestinal epithelial cells • Spreads in blood to the parenchymal cells of liver. no chronic carrier state. fever. • All non-lethal cases resolve. pale feces and jaundice common.

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Epidemiology • Globally distributed with differing rates of prevalence • Most common in developing countries .

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• Inactivated hepatitis A vaccine made from cell culture – 1995. . Prevention and control • Secretory IgA is important in protection from rhinovirus infections.