Orthomyxoviruses and Paramyxoviruses PDF

ORTHOMYXOVIRUSES AND PARAMYXOVIRUSES Dr. Upendo Kibwana Microbiology and Immunology Department MUHAS OUTLINE Orthomyxovirus – Viral properties, biological properties, antigenic structure. – Classification and Antigenic types – Epidemiology – Replicat...

ORTHOMYXOVIRUSES AND PARAMYXOVIRUSES Dr. Upendo Kibwana Microbiology and Immunology Department MUHAS OUTLINE Orthomyxovirus – Viral properties, biological properties, antigenic structure. – Classification and Antigenic types – Epidemiology – Replication and Pathogenesis – Clinical manifestations Paramyxovirus ORTHOMYXOVIRUES  Introduction Includes influenza viruses They are distributed worldwide and originates as zoonotic infections, carried by several species of birds and mammals Two major proteins; the matrix protein (M) and nucleoprotein (NP) distinguishes these viruses  General Properties Virion: Spherical, pleomorphic, Envelope: Contains viral 80–120nm in diameter hemagglutinin and helical nucleocapsid neuraminidase proteins Composition: RNA (1%), Replication: Nuclear protein (73%), lipid (20%), transcription; particles carbohydrate(6%) mature by budding from plasma membrane Genome: ss RNA, segmented, negative-sense,13.6kb overall size Outstanding characteristics: Proteins: Nine(9) structural Genetic reassortment proteins, one common among members of (1)nonstructural the same genus  Antigenic Drift and Antigenic Shift Two surface antigens of influenza undergo antigenic variation independent of each other  Antigenic drift:- gradual change in antigenicity caused by point mutations that affect major antigenic sites on the glycoprotein – a virion can escape recognition by the host’s immune system  Antigenic shift an abrupt change caused by genetic reassortment with an unrelated strain Influenza B and C viruses do not exhibit antigenic shift because few related viruses exist in animals  Classification and Nomenclature Orthomyxovirus genus belongs to Orthomyxoviridae family Genus consists of Influenza type A,B and C classified based on variation in the nucleoprotein antigen -no serologic cross reactivity In types A and B the hemagglutinin and neuraminidase antigens undergo genetic variation – the basis for the emergence of new strains Type C is antigenically stable  Nomenclature Nomenclature system for influenza virus isolates includes the following information: type, host of origin, geographic origin, strain number, and year of isolation Antigenic descriptions of the HA and the NA are given in parentheses for type A The host of origin is not indicated for human isolates,  Nomenclature cont…. Examples From human: A/HongKong/03/68(H3N2) From animals: A/swine/Iowa/15/30(H1N1) 15 subtypes of HA (H1–H15) and nine subtypes of NA (N1–N9), in many different combinations, have been recovered from birds, animals, or humans  Orthomyxoviruses Nomenclature. Human influenza virus Influenza A/Bangkok/1/79(H3N2) Influenza A/Singapore/1/57(H2N2) Influenza B/Ann Arbor/1/86 Influenza type Year of isolation Hemagglutinin subtype A/Sydney/5/97 (H3N2) Geographic source Isolate number Neuraminidase subtype  EPIDEMIOLOGY Estimated that annual epidemics of seasonal influenza cause 3–5 million cases of severe illness and 250,000–500,000 deaths worldwide – incidence of influenza peaks during the winter Influenza C least significant->causes mild, sporadic respiratory disease but not epidemic influenza Yearly epidemics are caused by both type A and type B viruses The rare, severe influenza pandemics are always caused by type A virus  Replication and Pathogenesis  Pathogenesis Transmitted from person to person primarily in droplets released by sneezing and coughing Inhaled virus lands in the lower respiratory tract where primary site of disease is the tracheobronchial tree – nasopharynx is also involved Neuraminidase of the viral envelope act on the N-acetylneuraminic acid residues in mucus to produce liquefaction – liquified mucus helps spread the virus through the respiratory tract  Pathogenesis…cont Infection of mucosal cells results in cellular destruction and desquamation of the superficial mucosa Cells die, in part due to the direct effects of the virus &possibly due to the effects of interferon. – at later times may also result from the actions of cytotoxic T-cells Viral damage to the respiratory tract epithelium lowers its resistance to secondary bacterial invaders, especially staphylococci, streptococci, and Haemophilus influenzae. Viremia is rare, so these systemic symptoms are not caused directly by the virus. – Circulating interferon possible cause  Clinical Findings Uncomplicated influenza; Fever (38 - 40 0C) Myalgias, headache, Ocular symptoms - photophobia, tears, ache, Dry cough, nasal discharge  H1N1 may gives rise to gastro- intestinal symptoms Pulmonary complications, sequelae: A. Croup in young children - symptoms include cough (like a barking seal), difficulty breathing, stridor (crowing sound during inspiration) B. Pneumonia-a complication of influenza A virus infection usually occur only in elderly adults and debilitated individuals, can be viral, secondary bacterial, or a combination of the two C. Reye Syndrome An acute encephalopathy of children and adolescents, usually between 2 and 16 years of age A rare complication of influenza B, influenza A, and herpesvirus varicella- zoster infections  Immunity Immunity to influenza is long lived and subtype specific Protection correlates with both serum antibodies and secretory IgA Antibodies against the ribonucleoprotein are type specific and are useful in typing viral isolates(A,B&C) The three types of influenza viruses are antigenically unrelated and therefore induce no cross-protection  Laboratory Diagnosis Detection of viral RNA; RT-PCR Isolation of the virus- embryonated eggs and primary monkey kidney cells can be used Detection of viral antigens-by using fluorescent or in enzyme immunoassays (ELISA) Serology- most common, complement fixation, hemagglutination inhibition, and immunodiffusion and enzyme-linked immunosorbent assay Specimen; nasal washings, gargles, and throat swabs  PREVENTION AND TREATMENT 1. Vaccines Updated annually to match circulating strains (usually trivalent or quadrivalent, targeting two Influenza A strains and one or two Influenza B strains) – Inactivated Influenza Vaccine: Given via injection – Live Attenuated Influenza Vaccine : Administered as a nasal spray (not recommended for certain groups like immunocompromised individuals) Pandemic Influenza Vaccines: Developed for specific pandemic strains (e.g., H1N1 vaccine in 2009). 2. Antiviral medication Antivirals can be used for both treatment and prophylaxis in high-risk individuals Neuraminidase Inhibitors: e.g Oseltamivir (Tamiflu), Zanamivir (Relenza), Peramivir Endonuclease Inhibitors: Baloxavir marboxil (Xofluza) PARAMYXOVIRUSES  Introduction They include the most important agents of respiratory infections of infants and young children The causative agents of two of the most common contagious diseases of childhood (mumps and measles) WHO estimates that acute respiratory infections and pneumonia are responsible every year worldwide for the deaths of 4 million children younger than 5 years of age  Characteristics Virion: Spherical, pleomorphic, 150 nm or more in diameter (helical nucleocapsid, 13 or 18 nm) Composition: RNA (1%), protein (73%), lipid (20%), carbohydrate (6%) Genome: ss RNA, linear, non-segmented, negative sense, non-infectious, about 15 kb Proteins: Six–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  Classification Paramyxoviridae family is divided into two subfamilies and seven genera, six of which contain human pathogens Most of the members consist of a single serotype Classification and Antigenic Types Parainfluenza serotypes are now recognized: 1, 2, 3, and 4 – Type 4 occurs in two subtypes (A and B), which possess common internal but different capsid antigens Serotypes belongs to two genera; Respirovirus (HPIV-1 and HPIV-3) and Rubulavirus (HPIV-2 and HPIV-4)  EPIDEMIOLOGY Major cause of lower respiratory tract disease in young children Type 3 is most prevalent;2/3 of infants infected during the first year of life Infections with types 1 and 2 occur at a lower rate Type 3 is endemic, (some increase during the winter) types 1 and 2 tend to cause epidemics during the fall or winter, frequently on a 2-year cycle Predisposing factors, including malnutrition, overcrowding, vitamin A deficiency, and environmental smoke or toxins.  Pathogenesis and Pathology Parainfluenza virus replication in the immunocompetent host appears to be limited to respiratory epithelia – Viremia, is uncommon. Severity of disease is affected by; susceptibility of the viral protein to cleavage by different proteases, production of an appropriate protease by host cells, immune status of the patient, and airway hyperreactivity virus-specific IgE antibodies produced during primary infections has been associated with disease severity-release of mediators of inflammation that alter airway function.  Clinical Findings Primary infections in young children usually result in rhinitis and pharyngitis; often with fever and some bronchitis children with primary infections caused by parainfluenza virus type 1, 2, or 3 may have serious illness – laryngotracheitis and croup (types 1 and 2 ) mainly between for children 6-18 months and bronchiolitis and pneumonia (type 3)mainly for peaks mainly from January to March Both RSV subgroups A and B circulate during these epidemics. – probably introduced into families by schoolchildren undergoing re-infection  Pathogenesis and Pathology Initially replication in epithelial cells of the nasopharynx. The virus spreads both extracellularly and by fusion of cells to form syncytia Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. – Viremia occurs rarely if at all. Narrow airways of very young infants are more readily obstructed by inflammation and edema IP is 3–5 days; Viral shedding may persist for 1–3 weeks from infants and young children, only 1–2 days from adults  Clinical Findings Ranges the common cold through pneumonia in infants to bronchiolitis in very young babies. – Bronchiolitis distinct clinical syndrome associated with this virus Pneumonia; develops in about half of infected immunocompromised children and adults Children who have had RSV bronchiolitis and pneumonia as infants often exhibit recurrent episodes of wheezing illness for many years Reinfection common in both children and adults – usually limited to the upper respiratory tract. Superimposed infection on preexisting disease, such as congenital heart disease->mortality rate may be high RSV is an important cause of otitis media  Laboratory diagnosis Similar methods as for diagnosis of parainfluenza viruses -RT-PCR -Viral antigen detection Hemagglutination or hemadsorption assays can not be used  Treatment and Prevention Relies primarily on supportive care (eg, removal of secretions, administration of oxygen). Ribavirin approved for infants at high risk for severe disease(aerosol). No vaccine is available today. Control measures same as described for parainfluenza viruses  MUMPS VIRUS Structure Shares many structural properties with the other paramyxoviruses Classification and Antigenic Type occurs only in a single serotype and shares minor common envelope antigens with other Paramyxovirus species Nucleotide-sequence homology between various mumps virus isolates is 90 to 99 %  Epidemiology Mumps occurs worldwide throughout the year in hot climates and peak in the winter and spring in temperate climates – Humans are the only known hosts. Local outbreaks are common in institutions, boarding schools, and military camps Quite contagious; most susceptible individuals in a household will acquire infection from an infected member  Pathogenesis The infecting virus probably enters the body through the pharynx or the conjunctiva. – Local multiplication in epithelial cells at the portal of entry and a primary viremia ->lasting 2 to 3 days The virus is carried to the main target organs (various salivary glands, testes, ovaries, pancreas, and brain) replication takes place in the ductal cells of the glands virus spreads to the central nervous system by unknown mechamism Shedding of the virus in salivary gland, conjunctival secretions and urine begins about 6 days before onset of symptoms and continues for another 5 days. virus may be recovered from blood During the first 2 days of illness and detected in CSF and cells during  Clinical Findings At least one-third of all mumps infections are subclinical Most characteristic feature of symptomatic cases is dematous, painful enlargement of one or both of the parotid glands (in 50% of cases) – Commonly, the submandibular salivary glands are involved CNS involvement common (in 10–30%of cases) causing aseptic meningitis – more common among males than females. Epididymo-orchitis develops in 23% of infected postpubertal males and Oophoritis develops in 5 % of infected postpubertal women  Diagnosis Typical cases involving the salivary glands can usually be made on the basis of clinical findings Etiologic diagnosis of other clinical manifestations without parotitis include – Detection of viral nucleic acid by RT-PCR. – Isolation of infectious virus. – serology. Treatment, Prevention, and Control There is no specific therapy An effective attenuated live-virus vaccine is available in combination with measles and rubella (MMR) live-virus vaccines. – recommended for all children at 12 to 18 months of age in many countries isolating patients with typical symptoms does little to prevent spread – degree of viral shedding before clinical symptoms and the 35% rate of subclinical infection  Refferences Brooks, Butel, Morse :Jawetz, Melnick, & Adelberg's Medical Microbiology 22nd Edition (2001) Patrick R. Murray,Medical Microbiology 4th edition Samual Barron.Medical Microbiology. 4th edition.y