PowerPoint Presentation

Paramyxoviridae

For 3rd Year MLS StudentsPrepared By Wondmagegn D.(MSC.)

1ObjectivesExplain the properties of Paramyxovirus Describe the pathogenesis and clinical features Paramyxovirus infectionIllustrate epidemiology ParamyxovirusDescribe the diagnosis Paramyxovirus infection2OutlineIntroductionStructure and replicationPIVMeasles VirusMumps VirusRSV

3IntroductionVirion- Spherical, Pleomorphic, 150-300 nmEnveloped virus : do not form such prominent spikes as on influenza virus 2 glycoproteins : viral hemagglutinin (HN) and Fusion (F)ss RNA, linear, non segmented, negative sense, 16-20 kb Replication- cytoplasmic, bud from plasma membraneThey are similar in many respects to orthomyxoviruses but are larger and do not have the segmented genome of the influenza viruses .4ContThe family Paramyxoviridae consists of three genera: Paramyxovirus, which includes the parainfluenza viruses and mumps virus; Pneumovirus, which includes respiratory syncytial virus; and Morbillivirus, which includes the measles virus.

Their virions have similar morphologies and protein components, and they share the capacity to induce cell-cell fusion (syncytia formation and multinucleated giant cells).

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Table 59-1Cont67GENUSGLYCOPROTEINSTYPICAL MEMBERSParamyxovirusHN, FHPIV1, HPIV3RubulavirusHN, FHPIV2, HPIV4, mumps virusMorbillivirusH, Fmeasles virusPneumovirus G, Frespiratory syncytial virusMetapneumovirusG, Fmetapneumoviruses Recent ClassificationPARAMYXOVIRUS SUBFAMILYPNEUMOVIRUS SUBFAMILY7ContThese agents cause some well-known major diseases. Measles virus causes a potentially serious generalized infection characterized by a maculopapular rash ( rubeola). Parainfluenza viruses cause upper and lower respiratory tract infections, primarily in children, including pharyngitis, croup, bronchitis, bronchiolitis, and pneumonia. Mumps virus causes a systemic infection whose most prominent clinical manifestation is parotitis.RSV causes mild upper respiratory tract infections in children and adults but can cause life-threatening pneumonia in infants.

8ContParamyxoviruses earlier grouped with Orthomyxoviruses because of HA and NA activities but they do have the following differencesRNA non segmentedRNA is RNase resistantTranscription of viral RNA in cytoplasmFusion of virus with cell membraneGenetic reassortment-rare

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Structure and ReplicationParamyxoviridae typically consist of a helical nucleocapsid, surrounded by an envelope that contains two types of integral membrane or envelope proteins.

The first, the HN protein (H stands for hemagglutinin, and N for neuraminidase), is involved in the binding of the virus to a cell; measles virus lacks the neuraminidase activity.

The second, the F protein (F stands for fusion), functions to fuse viral and cellular membranes, thus facilitating virus entry into the cytoplasm where viral replication occurs11ContEnvelope GlycoproteinsHN glycoprotein HN - hemagglutinin + neuraminidase activities Parainfluenza viruses Measles - referred to as H protein - no neuraminidase activity; RSV - G protein - neither activity.FUSION (F) Protein infection and pathogenesis- fusion of viral envelope with plasma membrane of host cell cell to cell fusion12Cont13

14M proteinhelical nucleocapsid (RNA plusNP protein) HN/H/G glycoprotein SPIKESpolymerasecomplexlipid bilayer membrane F glycoprotein SPIKESContpleomorphic1415VirusHNFusion proteinMeasles virus+-+mumps+++RSV--+Parainfluenza+++ReplicationReplication of the paramyxovirus genome, takes place in the cytoplasm of the host cell. Virus attaches to host cell surface receptors through HN, H or G glycoproteins.Fusion with the plasma membrane; ribonucleocapsid is released in the cytoplasm. The RNA of the virus is translated into positive sense RNA through use of the enzyme RdRp, which is short for RNA-dependent-RNA-polymerase. The positive sense RNA can then act as mRNA which is read by the host cell, and the host cells mechanisms build the necessary proteins, as well as gets copied into more negative sense RNA to use in the daughter virus.16Cont17

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18Parainfluenza virusViruses that usually cause mild cold like symptoms but can also cause serious respiratory tract disease.Four serologic types within the parainfluenza genus are human pathogens. Serologic types 1, 2,and 3 are second only to RSV as important causes of severe lower respiratory tract infection in infants and young children. They are especially associated with laryngotracheobronchitis (croup). Type 4 causes only mild upper respiratory tract infection in children and adults.limited to U.R.T. (no viremia)19ContTransmissionAerosols-Person to person contactIP 2-6 daysWide distributionType 3 most prevalent- pneumonia infantsType 1 and 2 croup infantsMost children get infection-no serologic variation-rare infection in adults.

20PathogenesisInfect epithelial cells of URTThe virus replicates more rapidly than measles and mumps viruses and can cause giant cell formation and cell lysis.Unlike measles and mumps rarely viremiaThe viruses generally stay in the upper respiratory tract, causing only cold like symptoms. In approximately 25% of cases, the virus spreads to the lower respiratory tract, and in 2% to 3%, disease may take the severe form of laryngotracheobronchitis.Death rare

21PIV EpidemiologyParainfluenza viruses are ubiquitous, and infection is common. The virus is transmitted by person to person contact and respiratory droplets.Primary infections usually occur in infants and children younger than 5 years. Reinfections occur throughout life, indicating short-lived immunity.Type 3 most prevalent

22Clinical Manifestations Croup (laryngotraheobroncitis) - most common manifestation of parainfluenza virus infection. However other viruses may induce croup e.g. influenza and RSV.Other conditions that may be caused by parainfluenza viruses include Bronchiolitis, Pneumonia, Flu-like tracheobronchitis, and Corza-like illnesses.2324

PIV Recovery

All infants- antibodies but not protectiveImmunity short livedCell mediated immunity both cell damage and confers protectionIgA protective but short livedAntibodies to F Neutralize prevent cell to cell spread Multiple serotypes and short live immunity Reinfection more common milder

25Laboratory DiagnosisDetection of Antigen - a rapid diagnosis can be made by the detection of parainfluenza antigen from nasopharyngeal aspirates and throat washings.Virus Isolation - Parainfluenza virus is isolated from nasal washings and respiratory secretions and grows well in primary monkey kidney cells.The presence of virus-infected cells in aspirates or in cell culture is indicated by the finding of syncytia and is identified with immunofluorescence.Serology - a retrospective diagnosis may be made by serology. CFT most widely used.Rapid RT-PCR techniques are becoming the method of choice to detect and identify parainfluenza viruses from respiratory secretions.26

Infected cell fusion caused by paramyxoviridaeUninfectedInfected27PIV TreatmentRibavirin-promising-aerosol formExperimental- killed virus vaccine-good antibody titer - no protection.Subunit vaccines and Live attenuated vaccine-intranasal being tested.Careful monitoring of the upper airway.28MeaslesSingle serotype & Humans are the natural hostMeasles virus causes a potentially serious generalized infection characterized by a maculopapular rash (rubeola).

Measles, also known as rubeola, is one of the five classic childhood exanthems, along with rubella, roseola, fifth disease, and chickenpox.

Historically, measles was one of the most common and unpleasant viral infections, with serious potential sequelae.29

Measles30

31Clinical SyndromesMeasles is a serious febrile illness .The incubation period lasts 7 to 13 days, and the prodrome starts with high fever and CCC and Pcough, coryza, conjunctivitis, and photophobia. The disease is most infectious during this time.After 2 days of prodromal illness, the typical mucous membrane lesions known as Koplik spots appear.3233

Measles rash

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Measles pathogenesisFIGURE 59-3FIGURE 59-436

Laboratory Diagnosis

The clinical manifestations of measles are usually so characteristic that it is rarely necessary to perform laboratory tests to establish the diagnosis. The measles virus is difficult to isolate and grow, although it can be grown in primary human- or monkey-cell cultures. Respiratory tract secretions, urine, blood, and brain tissue are the recommended specimens. It is best to collect respiratory and blood specimens during the prodromal stage and until 1 to 2 days after the appearance of the rash. 37

Laboratory Diagnosis

Measles antigen can be detected in pharyngeal cells or urinary sediment with immunofluorescence; the measles genome can be identified by reverse transcriptase polymerase chain reaction (RT-PCR) in either of the aforementioned specimens. Characteristic cytopathologic effects, including multinucleated giant cells with cytoplasmic inclusion bodies, can be seen in Giemsa stained cells taken from the upper respiratory tract and urinary sediment. Antibody, especially immunoglobulin M (IgM), can be detected when the rash is present.38The MMR Vaccine

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MUMPS

Mumps virus is the cause of acute, benign viral parotitis (painful swelling of the salivary glands). H and N + fusion protein on envelope spikesHumans are the natural host.thermolabileMumps is rarely seen in countries that promote use of the live vaccine, which is administered with the measles and rubella live vaccines.

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41Mumps clinical presentation42

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44Time course of Mumps infection

FIGURE 59-845

LABORATORY DIAGNOSIS

Virus can be recovered from saliva, urine, the pharynx, secretions from Stensens duct, and cerebrospinal fluid.Virus is present in saliva for approximately 5 days after the onset of symptoms and in urine for as long as 2 weeks.Mumps virus grows well in monkey kidney cells, causing the formation of multinucleated giant cells.Clinical diagnosis can be confirmed by serologic testing. A fourfold increase in the virus-specific antibody level or the detection of mumps-specific IgM antibody indicates active infection. Enzyme-linked immunosorbent assay, immunofluorescence tests, and hemagglutination inhibition can be used to detect the mumps virus, antigen,or antibody.46TREATMENT & PREVENTIONVaccines provide the only effective means for preventing the spread of mumps infection. Antiviral agents are not available.47Respiratory Syncytial VirusMost important cause of pneumonia and bronchiolitis in infantsFusion proteins- syncytia formationHumans and chimpanzees- natural host2 serotype: A & Bis a member of the Pneumovirus genus. 48lacks hemagglutinin and neuraminidase activities. It is the most common cause of fatal acute respiratory tract infection in infants and young children.It infects virtually everyone by 2 years of age, and reinfections occur throughout life, even among elderly persons.

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LABORATORY DIAGNOSIS

RSV is difficult to isolate in cell culture. The presence of the viral genome in infected cells and nasal washings can be detected by RT-PCR techniques, and commercially available immunofluorescence and enzyme immunoassay tests are available for detection of the viral antigen.53

TREATMENT & PREVENTION

In otherwise healthy infants, treatment is supportive, consisting of the administration of oxygen, intravenous fluids, and nebulized cold steam. Ribavirin, is administered by inhalation.Passive immunization with anti-RSV immunoglobulin is available for premature infants.Infected children must be isolated.No vaccine is currently available for RSV prophylaxis.54Summary StructureNegative sense ssRNA genome, helical nucleocapsid, envelope with attachment protein and F proteinPathogenesisTransmission in respiratory droplets and fusion of virus envelope via F protein with plasma membrane of cells in the respiratory tractReplication in cytoplasm, buddingViremia except for RSV and PIVinnate and antibody response important; many symptoms from immune response: rash in measles and swelling in mumps; PIV bronchitis and croup; RSV bronchiolitis and pneumonia in infantsSequelae in CNS for measles and mumps Diagnosis serology or nucleic acidMeasles Koplik spots; mumps swelling of parotid glandTreatment/preventionMMR live attenuated viral vaccine for measles and mumps, none for RSV or PIV5556

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