Picornaviridae Objectives Explain the properties of Picornavirus Describe

Picornaviridae

Objectives • Explain the properties of Picornavirus • Describe the pathogenesis and clinical features Picornavirus infection • Illustrate epidemiology Picornavirus • Describe the diagnosis Picornavirus infection

Acknowledgment • • Addis Ababa University Jimma University Hawassa University Haramaya University of Gonder American Society of Clinical Pathology(ASCP) Center for Disease Control and Prevention(CDC)

outline • • • Properties Classification and structure Pathogenesis Clinical features Diagnosis

Picornaviridae Picornaviruses : Enteroviruses Rhinovirus groups

Picornaviridae • Picornaviruses very large family but one of the smallest RNA containing viruses 8 -30 nm diameter

Picornaviridae • Most diverse (more than 200 serotypes) and 'oldest' known viruses-1400 BC • Very important humans and animals • Poliovirus • Hepatitis-A virus • Foot and Mouth diseases –animals • Human rhinoviruses-most important cause of common cold

Picornaviruses Human Enteroviruses • • Transient inhabitants of human alimentary tract More than 72 serotypes Polioviruses Coxsackieviruses Hepatitis A virus Echoviruses Very resistant to environment conditions, GI low p. Hfecal oral route

Picornaviruses Human Rhinoviruses • • At least 100 serotypes Major cause of common cold Sensitive to acidic p. H Replicate poorly above 33 C

Picornaviruses- Properties • • • Virion 28 -30 nm- non enveloped Icosahedral symmetry RNA 30 % + 67 % proteins MW 8 -9 million Genome : ss RNA, linear, positive sense 7. 2 -8. 4 kb Four capsid proteins VP 1 -AP 4 from cleavage of the original protomer VP 0 +single genome linke protein (VPg) One or two nonstructural proteins Replication and assembly in cytoplasm Infection: acute and cytolytic / persistent Insensitive to ether, chloroform and nonionic detergents p. H Enteroviruses stable 3 -5, Rhinoviruses-acid labile

Classification • Family – Picornaviridae- 6 Genera • 1. 2. 3. 4. 5. Genus Enterovirus* Rhinovius* Hepatovirus* Parechovirus* Apthovirus 6. Cardiovirus Type species Poliovirus Human rhinovirus Hepatitis A virus Human parechovirus Foot and mouth virus Encephalomycarditis virus

Enteroviruses of Human origin • Species: 1. Poliovirus 2. 3. Coxsackievirues of Group A Coxsackievirues of Group B 4. Echoviruses 5. Enteroviruses 6. Serotypes 3 serotypes 1 -24(no 23) 1 -6 1 -33 (no 10, 22, 23, 28) 68 -71 DP MONGA DMIP, FOM, AAU

New Enteroviruses Since 1969, 'new' Enteroviruses have been assigned numbers, not names • Pneumonia 68 • None (? ) 69 • Acute haemorrhagic conjunctivitis (1969 -1974 pandemic)70 • Meningitis, rhombencephalitis 71 • Hepatitis A virus (now a separate genus: Hepatovirus) 72

Poliomyelitis Poliovirus was once thought to be the main cause of paralysis before the advent of polio vaccines. Poliovirus account for a large portion of paralytic cases.

ENTEROVIRUS GROUP POLIOMYELITIS • “Acute infections that in its serious form affects the central nervous system. Destruction of motor neurons result in flaccid paralysis” • Most poliovirus infections are sub clinical

Poliomyelitis • • First described by Michael Underwood in 1789 First outbreak described in U. S. in 1843 21, 000 paralytic cases reported in the U. S. in 1952 Global eradication in near future Natural host only humans 3 antigenic types 1 -3 Permanent immunity to homologous type Heterotypic low degree resistance

Polyomavirus genome From Medical Microbiology, 5 th ed. , Murray, Rosenthal & Pfaller, Mosby Inc. , 2005, Fig. 52 -7.

Poliovirus • Typical Enterovirus (RNA) • Three serotypes: 1, 2, 3 • Minimal heterotypic immunity between serotypes • Rapidly inactivated by heat (55 C- 30 mts), formaldehyde, chlorine-(much higher concentrations needed) , ultraviolet light • No effect ether or chloroform or sodium deoxycholate • Narrowest tissue tropism (anterior horn cells of spinal cord, motor neurons, skeletal muscle cells, lymphoid cells)

Poliomyelitis Pathogenesis • Entry through mouth • Replication in pharynx, GI tract, local lymphatic • Hematologic spread to lymphatic and central nervous system • Viral spread along nerve fibers • Destruction of motor neurons

Polyomavirus pathogenesis From Medical Microbiology, 5 th ed. , Murray, Rosenthal & Pfaller, Mosby Inc. , 2005, Fig. 52 -8.

POLIO-CLINICAL • Incubation Period 3 days to 35 days Usually 7 -14 days • Asymptomatic infection, to mild fever, to severe and permanent paralysis

Polio-Clinical findings 1 Abortive poliomyelitis-most common form » Minor illness » Fever, malaise, drowsiness, head ache, nausea, » Vomiting, constipation, sore throat ↓ » Recovery few days 2 Nonparalytic poliomyelitis-aseptic meningitis » Symptoms As with type 1 » Stiffness and pain in back and neck » Diseases 2 -10 days recovery complete 3 Paralytic poliomyelitis » Lower motor neuron damage →Flaccid paralysis » Maximal recovery 6 months » Residual paralysis much longer

Polio-Clinical findings 4 Progressive Postpoliomyelitis Muscle Atrophy Symptoms may be seen decades after paralytic poliomyelitis (type 3) attack Most serious type – Permanent Paralysis and muscle wasting – Muscle atrophy – Loss of neuromuscular functions

Polio- Diagnosis • • • Recovery of virus throat swab/rectal swab Specimen frozen during transit Human / monkey cells Nt CPE 3 -6 days Serology: Very rarely used for diagnosis since cell culture is efficient Paired serum - Nt

Polio- Immunity • Infection-Permanent type specific • Low degree heterotypic • Passive immunity mother to offspring- maternal ab → disappears 6 months

Poliovirus Epidemiology • Reservoir Human • Transmission Fecal-oral Oral-oral possible • Communicability 7 -10 days before onset Virus present in stool 3 -6 weeks

Poliovirus Vaccine- history • 1955 Inactivated vaccine • 1961 Types 1 and 2 monovalent OPV • 1962 Type 3 monovalent OPV • 1963 Trivalent OPV • 1987 Enhanced-potency IPV (IPV)

Killed Polio Vaccine (Salk Vaccine) • Contains 3 serotypes of vaccine virus • Grown on monkey kidney (Vero) cells • Inactivated with formaldehyde • 4 inoculations over a period of 1 -2 yrs • Periodic boosters Only Ig. G

Live Oral Polio Vaccine (Sabin) • • • Contains 3 serotypes of vaccine virus Grown on monkey kidney or human diploid cells Stabilzed with Mag Chloride Shed in stool for up to 6 weeks following vaccination Problems: Storage, Mutation (type 2 and 3 mostly) Interference with other enteroviruses • Ig. G, Ig. A and Ig. M

Pediarix • Contains IPV, DTa. P, and hepatitis B vaccines • Minimum age 6 weeks, maximum age 6 years • Approved by FDA for first 3 doses of the IPV and DTa. P series • Not approved for booster doses

Polio Eradication • Last case in United States in 1979 • Western Hemisphere certified polio free in 1994 • Last isolate of type 2 poliovirus in India in October 1999 • Global eradication goal by 2005

Coxsackieviruses • typical enteroviruses • coxsackieviruses divided two groups on the basis of the lesions observed in suckling mice. • coxsackieviruses are distinguished from other enteroviruses by their pathogenicity for suckling rather than adult mice.

Coxsackieviruses – In mice CSV: – Group A viruses produce a diffuse myositis with acute inflammation and necrosis of fibers of voluntary muscles. • Group B viruses produce focal areas of degeneration in the brain, necrosis in the skeletal muscles, and inflammatory changes in the dorsal fat pads, the pancreas and occasionally myocardium.

Coxsackieviruses At least 29 immunological types • 23 group A and • 6 group B • Each has a type specific antigen.

COXSACKIEVIRUSES Clinical manifestations • Coxsackie viruses can cause polio-like paralytic disease • Coxsackie A – vascular lesions • Coxsackie B (body) mycarditis, pleurodynia

COXSACKIEVIRUSES Clinical manifestations • Neurologic: Aseptic meningitis • Skin and mucosa: Herpangia- a severe febrile pharyngitis (group A) • Hand-foot-and mouth diseases • Cardiac and Muscular disease (group B) • Ocular- Acute hemorrhagic conjunctivitis—A 24 • Respiratory: A 21, A 24, B 1, B 3 -5 • Gastrointestinal: diarrhea in children group A • Generalized disease of infants: Extremely seriousmultiple organs-rapid fatal

Hand-foot-and mouth disease(coxsackie A virus) DP MONGA DMIP, FOM, AAU

Herpangia • • • Severe febrile pharyngitis Coxsackie A virus (2 -6, 8, 10) No relation with herpes virus Abrupt onset Discrete vesicles on posterior half of palate Self limiting-small children

COXSACKIEVIRUSES Diagnosis • Isolation of virus : throat washings and stools ↓ – Tissue culture-CPE-5 -14 days/suckling mice – illness 3 -8 days group A 5 -14 days group B • Serology : Nt early phase, specific persist for years Serological tests difficult to evaluate – multiplicity of types

Echoviruses • human feces (enteric, cytopathic, human, orphan viruses). • More than 32 serotypes (types 1 -34; echovirus 10 and 28) -not all pathogenic • Monkey kidney cells/ He. La • Aseptic meningitis • Rashes types 4, 9, 16, 18 • Conjunctivitis • Infantile diarrhea • Muscle weakness etc

Cytopathic Effect (Virology Hospital) Laboratory, New-Yale Haven

Rhinoviruses • Common cold viruses • Mild URT illnesses • Nasal secretions, throat and oral secretions

Rhinoviruses-properties • • Picornaviruses similar to enteroviruses But inactivated low p. H More thermostable survive for days on surfaces Infect only humans, gibbons, chimpanzee Replication limited epithelium nasal mucosa In vitro Human cell lines-33 C More than 100 antigenic types

Rhinoviruses - clinical • • Common cold IP 2 -4 days Acute illness up to 7 days Sneezing, nasal obstruction, nasal discharge, sore throat, head ache, malaise, mild cough, little/ no fever Non productive cough-2 -3 weeks • No specific treatment/no vaccine

Foot-and-mouth disease Aphthovirus of cattle • Highly contagious disease cattle, sheep, pigs, goats ↓ • Humans • Fever, salivation, vasiclulization of mm oropharynx and skin of palms, soles, fingers and toes • Virus acid labile • At least 7 types 30 subtypes