Picornaviruses

 Represent a very large virus family with respect to the number of members  One of the smallest in terms of virion size and genetic complexity.  Include two major groups of human pathogens: 1- Enteroviruses : transient inhabitants of the human alimentary tract and may be isolated from the throat or lower intestine. 2- Rhinoviruses : isolated chiefly from the nose and throat.  Enteroviruses are stable at acid pH (3.0–5.0) for 1–3 hours, whereas rhinoviruses are acid-labile.  Many enteroviruses (polioviruses, echoviruses, some coxsackieviruses) can be grown at 37°C in human and monkey cells. Most rhinovirus strains can be recovered only in human cells at 33°C.

 However, subclinical infection is far more common than clinically manifest disease.  Diseases which are caused by many picornaviruses : severe paralysis,aseptic meningitis, pleurodynia, myocarditis, vesicular and exanthematous skin lesions, mucocutaneous lesions, respiratory illnesses, undifferentiated febrile illness, conjunctivitis, and severe generalized disease of infants.  The most serious disease caused by any enterovirus is poliomyelitis.

Members of the Picornaviridae Cause Many Serious Diseases of Man and Animals In geneneral : 9 genera Genus Enterovirus (human) - Poliovirus, 3 major types cause paralysis - Coxsackievirus(A, B): pathogenic for newborn mice - Echoviruse Genus Rhinovirus (human) - cause respiratory tract infections, acid labile, cause colds in humans (,,, types). Genus Hepatovirus (human) - Hepatitis A, contagious liver infections. Genus Cardiovirus - Cause encephalomyocarditis in mouse acid labile, source is a rodent reservoir. Genus Apthovirus - acid labile, foot and mouth disease, most destructive in Africa. Genus Parcheovirus (human) - similar to other enteroviruses, such as gastrointestinal and respiratory illness, meningoencephalitis, otitis media, and neonatal diseases.

 Poliomyelitis is an acute infectious disease that in its serious form affects the central nervous system. Antigenic Properties  There are three antigenic types of polioviruses. Pathogenesis & Pathology:  The mouth is the portal of entry of the virus, and primary multiplication takes place in the oropharynx or intestine.  It is believed that the virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer's patches, and the small intestine. The central nervous system may then be invaded by way of the circulating blood.

 The virus is regularly present in the throat and in the stools before the onset of illness.  Antibodies to the virus appear early in the disease, usually before paralysis occurs.

 Poliovirus can spread along axons of peripheral nerves to the central nervous system, where it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain.  Poliovirus does not multiply in muscle in vivo. The changes that occur in peripheral nerves and voluntary muscles are secondary to the destruction of nerve cells. Some cells that lose their function may recover completely.  In addition to pathologic changes in the nervous system, there may be myocarditis, lymphatic hyperplasia, and ulceration of Peyer's patches.

Clinical Findings:  When an individual susceptible to infection is exposed to the virus, the response ranges from in apparent infection without symptoms, to a mild febrile illness, to severe and permanent paralysis.  The incubation period is usually 7–14 days, but it may range from 3 to 35 days. 1.Mild Disease: o This is the most common form of disease. o The patient has only a minor illness, characterized by fever, headache, nausea, vomiting, and sore throat in various combinations. o Recovery occurs in a few days. 2. Nonparalytic Poliomyelitis (Aseptic Meningitis): o In addition to the symptoms and signs listed in the preceding paragraph, the patient with the nonparalytic form has stiffness and pain in the back and neck.

3. Paralytic Poliomyelitis:  The predominating complaint is flaccid paralysis resulting from lower motor neuron damage. 4. Progressive Postpoliomyelitis Muscle Atrophy: It is a specific syndrome and is rare. A result of physiologic and aging changes in paralytic patients already burdened by loss of neuromuscular functions.

Laboratory Diagnosis:  The virus may be recovered from throat swabs taken soon after onset of illness and from rectal swabs or stool samples collected over long periods.  Poliovirus is uncommonly recovered from the cerebrospinal fluid—unlike some coxsackieviruses and echoviruses.  Specimens should be kept frozen during transit to the laboratory.  Cytopathogenic effects appear in 3–6 days. An isolated virus is identified and typed by neutralization with specific antiserum. Virus can also be identified by polymerase chain reaction (PCR) assays.

 Epidemiology:  Poliomyelitis has had three epidemiologic phases: endemic, epidemic, and the vaccine era. The first two reflect prevaccine patterns.  Before global eradication efforts began, poliomyelitis occurred worldwide—year-round in the tropics and during summer and fall in the temperate zones. Winter outbreaks are rare.  children are usually more susceptible than adults because of the acquired immunity of the adult population.  The case fatality rate is variable. It is highest in the oldest patients and may reach 5–10%.

 Prevention & Control: Both live-virus and killed-virus vaccines are available.  Formalinized vaccine (Salk) is prepared from virus grown in monkey kidney cultures. Killed-virus vaccine induces humoral antibodies but does not induce local intestinal immunity so that virus is still able to multiply in the gut.  Oral vaccines contain live attenuated virus grown in primary monkey or human diploid cell cultures. The vaccine can be stabilized by magnesium chloride. The live polio vaccine infects, multiplies, and thus immunizes.  The vaccine produces not only IgM and IgG antibodies in the blood but also secretory IgA antibodies in the intestine, which then becomes resistant to reinfection.  Both killed-virus and live-virus vaccines induce antibodies and protect the central nervous system from subsequent invasion by wild virus.

 The vaccine viruses—particularly types 2 and 3—may mutate in the course of their multiplication in vaccinated children.  Live-virus vaccine should not be administered to immunodeficient or immunosuppressed individuals or their household contacts.  Immune globulin can provide protection for a few weeks against the paralytic disease but does not prevent subclinical infection. Immune globulin is effective only if given shortly before infection; it is of no value after clinical symptoms develop.

 They produce a variety of illnesses in humans, including aseptic meningitis and respiratory and undifferentiated febrile illnesses  Divided into two groups, A and B  Group A: Herpangina (vesicular pharyngitis), hand-foot-and-mouth disease, and acute hemorrhagic conjunctivitis  Group B: pleurodynia (epidemic myalgia), myocarditis, pericarditis, and severe generalized disease of infants.  More pathogenic than the echoviruses. Clinical Findings:  Incubation period of coxsackievirus infection ranges from 2 to 9 days.  Aseptic meningitis: Caused by all types of group B and by many group A viruses (A7 and A9). Fever, malaise, headache, nausea, and abdominal pain are common early symptoms.  Herpangina: Caused by certain group A viruses. There is an abrupt onset of fever and sore throat with discrete vesicles on the posterior half of the palate, pharynx, tonsils, or tongue.

 Hand-foot-and-mouth disease: Associated particularly with coxsackievirus A16. characterized by oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs  Pleurodynia: (epidemic myalgia) Caused by group B viruses. Fever and stabbing chest pain are usually abrupt in onset but are sometimes preceded by malaise, headache, and anorexia.  Myocarditis: An acute inflammation of the heart or its covering membranes (pericarditis). Coxsackievirus B infections are a cause of primary myocardial disease in adults as well as children.  Generalized disease of infants: Caused by group B coxsackieviruses. An extremely serious disease in which the infant is overwhelmed by simultaneous viral infections of multiple organs, including heart, liver, and brain.

 Laboratory diagnosis:  Nucleic Acid Detection  Serology  Epidemiology:  Found in all over the world  Isolated more in summer and early fall.  Share many properties with other enteroviruses, including the echoviruses and polioviruses.  Control:  No vaccines or antiviral drugs available for prevention or treatment of diseases caused by coxsackieviruses

 Echoviruses infect the human enteric tract Cause aseptic meningitis, encephalitis, febrile illnesses with or without rash, common colds, and ocular disease  Epidemiology:  Similar to that of other enteroviruses  Occur in all parts of the globe  More found in the young than in the old.  Five times more prevalent in children of lower-income families than in those living in more favorable circumstances.  Control:  No antivirals or vaccines (other than polio vaccines) available for the treatment or prevention of any enterovirus diseases.  Laboratory diagnosis:  Nucleic Acid Detection  Serology

 Rhinoviruses are the common cold viruses.  They are usually isolated from nasal secretions but may also be found in throat and oral secretions.  These viruses—as well as coronaviruses, adenoviruses, enteroviruses, parainfluenza viruses, and influenza viruses—cause upper respiratory tract infections, including the common cold syndrome. Classification:  Human rhinoviruses can be divided into major and minor receptor groups. I. The major group: use intercellular adhesion molecule-1 (ICAM-1) as receptor II. The minor group: bind members of the low-density lipoprotein receptor (LDLR) family.

Properties of the Virus: General Properties:  They are more thermostable than enteroviruses  These viruses are infectious only for humans, gibbons, and chimpanzees  They can be grown in a number of human cell lines, including the WI-38 and MRC-5 lines. Pathogenesis & Pathology:  There is a direct correlation between the amount of virus in secretions and the severity of illness.  Replication is limited to the surface epithelium of the nasal mucosa.

Clinical Findings:  The incubation period is brief from 2 to 4 days  The acute illness usually lasts for 7 days  Usual symptoms in adults include sneezing, nasal obstruction, nasal discharge, and sore throat, etc.  Secondary bacterial infection may produce acute otitis media, sinusitis, bronchitis, or pneumonitis, especially in children.  Antibody develops 7–21 days after infection  They be transmitted through close contact, by means of virus- contaminated respiratory secretions Treatment & Control:  No vaccine: - difficulty in growing rhinoviruses to high titer in culture - The multiplicity of serotypes causing colds

a hundred days of foot and mouth

 It may be transmitted to humans by contact or ingestion  In humans, the disease is characterized by fever, salivation, and vesiculation of the mucous membranes of the oropharynx and of the skin of the palms, soles, fingers, and toes.  Highly contagious disease of domestic and wild ruminants and pigs.  In the early stages of infection when viremia is present and when vesicles in the mouth and on the feet rupture and liberate large amounts of virus.  can be fatal in young animals – myocarditis  not usually fatal in adults but causes economic losses (trade implications)