Picornaviridae. Picornaviridae: They are small naked icosahedral, with ss RNA +ve polarity single molecule genome, size of virion ~28-30 nm. Classification.

Presentation on theme: "Picornaviridae. Picornaviridae: They are small naked icosahedral, with ss RNA +ve polarity single molecule genome, size of virion ~28-30 nm. Classification."— Presentation transcript:

1 Picornaviridae

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3 Picornaviridae: They are small naked icosahedral, with ss RNA +ve polarity single molecule genome, size of virion ~28-30 nm. Classification of Picornaviridae: This family contain Five genera : (1) Enterovirus. (2) Rhinovirus (3) Heparnavirus: Hepatitis A virus, HAV of monkeys. (4) Apthovirus: (Foot & mouth disease of cattle). (5) Cardiovirus: (Encephalomyocarditis virus and meningovirus; mouse encephalomyelitis virus).

4 Viral genome: The picoravirus genome is one piece of linear, single stranded positive sense RNA. The RNA is infectious and serves as its own messenger for protein translation. The virion is about 27 nm in diameter. General properties: The enteroviruses and cardioviruses are acid stable in contrast, the rhinoviruses and aphthoviruses are acid labile. The disease caused by picornaviruses range from paralytic poliomyelitis to aseptic meningitis, hepatitis, pleurodynia, myocarditis, skin rashes and common colds; inapparent infection is very common. Different viruses may produce the same syndrome; on the other hand, a single picornavirus may cause several different syndromes.

5 Enteroviruses: (EVs) subgroups includes: (1) Polioviruses: Three serotypes (1, 2, & 3). (2) Coxsackievirus A : 23 serotypes (1-22, & 24). (3) Coxsackievirus B: 6 serotyes (1-6). (4) Echoviruses: no. of serotypes 31 (1-7, 9, 11-27, 29-34). (5) Enterviruses: no. of serotypes 4 (68-71). Characteristics of Enteroviruses: Enteroviruses comprise 67 distinct serotypes with in the family Picornaviridae. The traditional taxonomic subgroups of EVs are based on the patterns of replication of the individual serotypes in host cells and tissues. Like other picornaviruses EVs are small 27 to 30 nm in diameter, consisting of a simple viral capsid and a single strand of positive sense RNA. EVs are acid and ether stable and grow optimally at core body temperature.

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7 Polioviruses: cause poliomyelitis, an acute infectious disease, that in its serious form affects the CNS, cause destruction of motor neuron of spinal cord result in flaccid paralysis; however, most poliovirus infection are sub- clinical. Epidemiology: Found worldwide, spreads rapidly in densely populated areas with poor sanitation. Infection occurs in summer & early fall months. Transmission of poliomyelitis is occurred via feco-oral route. Incidence & the severity of paralytic disease increase with the age of onset. As a result of mass vaccination, polio is now an almost extracted disease except in under developed countries.

8 Pathogenesis: A typical course of poliovirus infection begins with ingestion of the virus, followed by initial replication of the virus in oropharyngeal mucosa & intestinal mucosa ( virus is found in throat & shed in the feces). Then virus spread by lymphatic system (tonsils & payers patches) to the blood stream, forming a transient viremia, other susceptible extraneural tissue become infected, & sufficient virus now produced to establish persistent viremia which is responsible for hematogenous spread of the virus to CNS, where many types of cells have receptors for the virus including anterior horn cell of spinal cord, nerve cells in medulla & brain stem.

9 Clinical manifestation: 1-Inapparent infection: majority of poliovirus infections (90-95%) are subclinical & demonstrated by serology. 2-Abortive infection: ~ (4-8%) of poliovirus infections, here we have non specific symptoms ( fever, malaise, drowsiness, headache, nausea, vomiting, constipation & sore throat) without CNS involvement. 3-Aseptic meningitis: ~ 1 % of poliovirus infections presented with self limiting meningitis with no sequelae. 4-Paralytic poliomyelitis: ~ 0.1 % of patients develop paralytic poliomyelitis, this form of poliomyelitis is favored during infection by ( surgical trauma e.g tonsillectomy, injection, fatigue, pregnancy & increase age of the patients).

10 Paralytic poliomyelitis: involve the following forms: a-Spinal poliomyelitis: due to the involvement of anterior horn cells of spinal cords, characterize by asymmetrical flaccid paralysis of proximal muscles of the extremities. b-Bulbar poliomyelitis: much more serious, involve cells of medulla or brain stem; 6-25% of paralytic disease & this form more common in adults. c-Bulbospinal poliomyelitis:carry very poor prognosis. d-Encephalitis: as a result of poliovirus is very rare. e-Post polio syndrome: 20-30 % of those patients with paralytic poliomyelitis in their youth experience fatigue, muscle pain, weakness, & atrophy 25-30 years later, this recurrence seems to be associated with further denervation of previously affected group of muscles.

11 Immunity: Is permanent to the type cause the infection, passive immunity transfer from the mother to offspring & disappear in the 1st 6 month of life. Viral neutralization Ab. form soon after exposure to virus, often before onset of illness & persist for life. Prevention: two vaccine for poliomyelitis,(both contain 3 serotypes) 1-Killed vaccine(Salk):(IPV) The inactivated polio vaccine is administered parentally does not colonize the intestine, & cause only systemic (humoral) immune response, but does not induce local intestinal immunity. 2-Attenuated vaccine (Sabin):(OPV) Administered orally & have several advantages: (a) Oral immunization is simpler & more suitable for mass vaccination programs. (b) Both local & systemic immunity are induced. (c) Attenuated virus is transmitted by feco-oral route to non immunized individual. Disadvantages of Oral vaccine: Some paralytic poliomyelitis can be caused by the attenuated vaccine, which seems to have capacity to mutated to virulent forms upon replication in intestine but this is rather rare event, occurring once for every 2.6 million dose of oral vaccine.

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13 Coxsackieviruses: a large subgroup of enteroviruses, are divided into groups A and B on the basis of different pathogenic potentials for mice. Coxsackieviruses: Coxsackievirus A 23 serotypes ( 1-22, 24). Coxsackievirus B 6 serotypes (1-6). Coxsackievirus diseases : 1-Inapparent infection comprise > 90% of infections. 2-Upper respiratory infections (common cold) & undifferentiated febrile illness are common with totally non specific presentation. 3-Aseptic meningitis & meningoencephalitis. 4-Strain specific manifestations:

14 I-Coxsackie A viruses are most frequently associated with: (1)-Infantile diarrhea: serotypes 18, 20-22, & 24. (2)-Herpangina: Serotypes 1-6, 8, 10,and 22 herpetic lesion on the posterior pharynx with abrupt fever & sore throat. (3)-Hand-foot and mouth disease: Serotypes 16 but 5, & 10 can also cause such type of infection. It is self limiting disease, characterize by oral & pharyngeal ulceration with vesicular rash of the palms & soles that may spread to the arms & legs, vesicles heals without crust.

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16 II-Coxsackie B viruses (a)-Myocarditis & pericarditis all serotypes ( particularly B5), may be fatal in neonates or may cause permanent heart damage. (b)-Multi systemic disease of newborn stereotype 2-5, here neonate present with encephalomyocarditis syndrome, hepatitis, & adrenal cortex involvement, multisystemic disease of the new born is associated with high morbidity & mortality rate. (c)-Pleurodynia,( Bornholm disease, epidemic myalgia) all serotypes, characterize by painful inflammation of intercostal muscles & to lesser extent the pleura usually accompanied with fever. (d)-Chronic fatigue syndrome all serotypes, the patients have incapacitating fatigue of long duration (6 month or longer) without identified physical cause.

17 Echoviruses ( enteric cytopathogenic human orphan viruses) group together because they infect the human enteric tract and they can be recovered from humans only by inoculation of certain tissue cultures, these viruses where isolated from stool of healthy children, there are 31 serotypes (1-7, 9, 11-27, 29-34).) Clinical diseases: (1) Common cold: like other enteroviruses cause URTI, & undifferentiated febrile illness. (2) Aseptic meningitis:Echoviruses are most common cause of aseptic meningitis in US, with moderate severity of symptoms & mental state of patients remain clear. (3) Ascending paralysis or encephalitis: rare echoviruses cause poliomyelitis like ascending paralysis or encephalitis. (4) Boston exanthema:infection with type 9, 16 echoviruses, is associated with morbiliform rash. (5) Infantile diarrhea: echovirus 18 associated with diarrhea.

18 Diagnosis: Isolation of EVs in tissue culture remain the gold standard for diagnosis. Coxsackievirus type A serotypes able to replicate in suckling mice, with resultant diffuse myositis and flaccid paralysis; however, these viruses were not readily grown in tissue culture cells derived from monkey or human tissues. Coxsackievirus type B grow in tissue cultures of both simian and human origin as well as suckling mice, the pathology in type B differ, myositis here is focal and direct infection of the brain, myocardium, pancreas and liver also occurs. The echovirus were defined by their ability to grow only in simian derived tissue culture cells but not at all in animal systems. The polioviruses grow more prolifically in cells of human and simian origins and in monkeys; they don’t grow in murine models.

19 Serologic diagnosis: had only a limited role in EV diagnosis because of the great diversity of EV serotypes and the lack of a single common antigen. Three types of antibody determination applied to the EVs 1-neutrilization. 2-complement fixation test. 3-hemagglutination inhibition.

20 Rhinoviruses

21 Rhinovirus are differentiated from enteroviruses by their loss of infectivity upon exposure to pH 3 for 3 h at room temperature. At present, more than 100 rhinovirus serotypes have been numbered on the basis of neutrilization tests. Rhinoviruses can be divided into two groups based on binding to cell receptors. Intracellular adhesion molecule 1 (ICAM-1) is the cell receptor for the majority ( major group) of rhinovirus, or approximately 90% of serotypes. The minor group receptor has been identified as a 120 kDa cell surface protein of unknown function. Rhinovirus type 87 appears to utilize neither the major nor the minor group receptor.

22 Pathogenesis: Rhinoviruses are spread by aerosols & infect the upper respiratory tract. They can also be spread by fomites such as hands & other forms of direct contact.fomites Rhinoviruses are quite stable, lasting for hours on fomites, but they are sensitive to temperature, for that reason they do not spread to the lower respiratory tract cuase they replicate best at a few degrees below normal body temperature. Although the most common route of infection is the nose, virus can also enter via the mouth & the eyes. There is usually no gastrointestinal involvement because of the acid liability of the virus. Rhinovirus produce very localize infection in upper respiratory tract without any detectable viremia, so the virus commonly found in throat & nose but not isolated from feces. The virus has short incubation period 2-4 days, then followed by typical localize infection involve surface epithelium & submucosa of upper respiratory tract.

23 Clinical diseases: (COMMON COLD) Rhinoviruses are the most frequent etiologic agents of common cold. After incubation period 2-4 days, [ patient infectious from right before onset of symptoms till approximately 2-3 days of the illness]. Disease manifestation in adults: sneezing, nasal obstruction, nasal discharge, & sore throat, headache, mild cough, malaise, chilly sensation, with low grade fever. This acute illness usually lasts for 7 days although non productive cough may persist for 2-3 weeks. Complication include bronchitis, pneumonia specially in children, otitis media, or sinusitis. Diagnosis: (a) Clinically (b) Culture & isolation nasal secretion are the best specimens for the isolation of virus. Treatment: supportive, unless those had 2nd bact. infection