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paramyxovirus

الكلية كلية الصيدلة القسم فرع البايولوجي المرحلة 2
أستاذ المادة سماح احمد كاظم الجبوري 4/10/2011 9:10:38 AM

Paramyxoviruses

The paramyxoviruses include the most important agents of respiratory infections of infants and young children (respiratory syncytial virus and the parainfluenza viruses) as well as the causative agents of two of the most common contagious diseases of childhood (mumps and measles). The World Health Organization estimates that acute respiratory infections and pneumonia are responsible every year worldwide for the deaths of 4 million children under 5 years of age. Paramyxoviruses are the major respiratory pathogens in this age group.

All members of the Paramyxoviridae family initiate infection via the respiratory tract. Replication of the respiratory pathogens is limited to the respiratory epithelia, whereas measles and mumps become disseminated throughout the body and produce generalized disease.

Rubella virus, though classified as a togavirus because of its chemical and physical properties, can be considered with the paramyxoviruses on an epidemiologic basis.

Properties of Paramyxoviruses can be summarized as following:

Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13–18 nm)

Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%)

Genome: Single-stranded RNA, linear, nonsegmented, negative-sense, noninfectious, about 15 kb

Proteins: Six to eight structural proteins

Envelope: Contains viral glycoprotein (G, H, or HN) (which sometimes carries hemagglutinin or neuraminidase activity) and fusion (F) glycoprotein; very fragile

Replication: Cytoplasm; particles bud from plasma membrane

Outstanding characteristics:

Antigenically stable

Particles are labile yet highly infectious

Characteristics of Genera in the Subfamilies of the Family Paramyxoviridae.

ParamyxovirinaePneumovirinae

PropertyRespirovirus Rubulavirus Morbillivirus Henipavirus^{1
Pneumovirus Metapneumovirus}

Human virusesParainfluenza 1, 3Mumps, parainfluenza 2, 4a, 4bMeaslesHendra, NipahRespiratory syncytial virusHuman metapneumovirus

Serotypes1 each1 each1?2?

Diameter of nucleocapsid (nm)181818?1313

Membrane fusion (F protein)++++++

Hemolysin2
+++?00

Hemagglutinin3
+++000

Hemadsorption+++000

Neuraminidase3
++0000

Inclusions4
CCN,C?C?

^{1Zoonotic paramyxoviruses.
2Hemolysin activity carried by F glycoprotein.
3Hemagglutination and neuraminidase activities carried by HN glycoprotein of respiroviruses and rubulaviruses; H glycoprotein of morbilliviruses lacks neuraminidase activity; G glycoprotein of other paramyxoviruses lacks both activities.
4C, cytoplasm; N, nucleus..}

^{Parainfluenzaviruses and RSV produce acute respiratory diseases . morbilliviruses and mumps systemic disease = diversity! They also differ from ^{Orthomyxoviruses}^{genetically - non-segmented genome with little genetic variation}}

^{Morphology:
Glycoproteins - do not form such prominent spikes as on influenza virus:

· N – the nucleocapsid protein associates with genomic RNA (one molecule per hexamer) and protects the RNA from nuclease digestion
· P – the phosphoprotein binds to the N and L proteins and forms part of the RNA polymerase complex
· M – the matrix protein assembles between the envelope and the nucleocapsid core, it organizes and maintains virion structure
· F – the fusion protein projects from the envelope surface as a trimer, and mediates ^{cell entry}^{by inducing fusion between the viral envelope and the cell membrane by class I fusion.}

· H/HN/G – the cell attachment proteins span the viral envelope and project from the surface as spikes. They bind to proteins on the surface of target cells to facilitate cell entry. Proteins are designated H (^{hemagglutinin}^{) for morbilliviruses and henipaviruses as they possess}^{haemagglutination}^{activity, observed as an ability to cause red blood cells to clump. HN (}^{Hemagglutinin-neuraminidase}^{) attachment proteins occur in respiroviruses, rubulaviruses and avulaviruses. These possess both haemagglutination and}^{neuraminidase}^{activity which cleaves sialic acid on the cell surface, preventing viral particles from reattaching to previously infected cells. Attachment proteins with neither haemagglutination nor neuraminidase activity are designated G (}^glycoprotein^{). These occur in members of pneumovirinae.}
· L – the large protein is the catalytic subunit of ^{RNA-dependent RNA polymerase}^(RDRP)

· Accessory proteins – a mechanism known as RNA editing allows multiple proteins to be produced from the P gene. These are not essential for replication but may aid in survival in vitro or may be involved in regulating the switch from mRNA synthesis to antigenome synthesis.}

^{Replication:
Very similar for all viruses in this group. Unlike influenza, all the action occurs in the cytoplasm. However, the overall strategy very similar to influenza, although unlike influenza, Paramyxovirus replication is resistant to actinomycin D.

A large excess of nucleocapsids are produced in infected cells, which form characteristic cytoplasmic inclusion bodies. Syncytium formation is quite common (F glycoprotein).

Parainfluenzaviruses 1-4:
Cause acute respiratory infections of man ranging from relatively mild influenza-like illness to bronchitis, croup (narrowing of airways which can result in respiratory distress, due to swelling of the larynx and related structures ) and pneumonia; common infection of children. Transmitted by aerosols. Little serological variation, therefore rare infection in adults
Treatment & Prevention:The antiviral drug ribavrin has been used that blocked the capping the viral mRNA which can be prevented by the used of subunit vaccine & live attenuated vaccine
Mumps:}

^{Recognized by the ancient Greeks, virus first isolated in 1934. Haemagglutination is a valuable assay technique for this virus. Humans are believed to be the only natural reservoir for the virus (possibly primates). Transmission via saliva and respiratory secretions; less infectious than measles/chickenpox - more adult cases.
Symptoms: typically causes painful swelling of parotid glands 16-18 days after infection. This is preceded by primary replication of the virus in epithelial cells of the URT and local lymph nodes, followed by viraemia. .

· Prevention: one invariant serotype therefore vaccines are viable - both formalin-inactivated and live attenuated exist, the latter now being widely used

Treatment: none (passive immunization has been used).}

^Measles:

^{Measles virus is believed to have evolved from ^rinderpest^{(or a similar animal virus) 4000-5000 years ago - when Babylonian cities grew large enough to support continuous person-to-person transmission and thus maintain the virus. One of the most infectious diseases known! ~500,000 deaths in children in the third world - part of the W.H.O. expanded programme of immunization. Childhood infection almost universal, protection resulting from this is probably lifelong. Both man and wild monkeys are commonly infected, but the virus can also infect rodents (in wild?). In culture, produces characteristic intranuclear inclusion bodies and syncytial giant cells. Transmission and initial stages of disease similar to mumps, but this virus can also infect via the eye and multiply in the conjunctivae. Viraemia following primary local multiplication results in widespread distribution to many organs.}}

^{Symptoms: After a 10-12 day incubation period, dry cough, sore throat, conjunctivitis (virus may be excreted during this phase!), followed a few days later by the ^{characteristic red, maculopapular rash}^and^{Koplik s spots}^{- raised red spots with white centres in the mouth..
Complications include bronchopneumonia and otitis media (with or without secondary bacterial infections) (relatively common), and encephalitis.
Subacute schlerosing pan encephalitis (SSPE).}

Treatment: Vitamin A & The antiviral drug ribavrin has been used
Prevention: Both live and killed vaccines exist.

Respiratory syncytial virus (RSV):}

^{RSV was first isolated in 1956 and subsequently recognized as a major cause of L.R.T. disease in infants and young children. causing bronchitis, pneumonia and croup. RVS has been suggested as a possible factor in cot death and asthma.}

^{RSV may be linked to epidemics of asthma and has been identified as an exacerbating factor in nephrotic disease, cystic fibrosis, and opportunistic infections in the immunocompromised. Bone marrow transplant patients develop lower respiratory tract disease with RSV,).
Treatment & Prevention:The antiviral drug ribavrin has been used Currently no effective vaccine
Human Metapneumovirus (HMPV):
HMPV was first isolated from children in the Netherlands and assigned to the pneumovirus genus on the basis of clinical data, sequence homology and gene organization. HMPV produces RSV-like illnesses in children, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia.). All recent data suggests that hMPV infections are not limited to young children or to the upper respiratory tract and that this virus causes severe lower respiratory tract diseases in high-risk subjects.

Nipah and Hendra Viruses:
^Nipah^and^Hendra^{viruses have emerged as new pathogens in Malaysia and Australia respectively in recent}}

المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .