Viral Infections of the Respiratory System

1. Viral Infections of the Respiratory System

2. Clinical manifestations • Common cold (rhinitis) • Pharyngitis • Tonsilitis • Sinusitis & otitis media • Croup (acute laryngotracheobronchitis) • Acute bronchitis • Acute bronchiolitis • Viral pneumonia • Influenza (Flu)

3. The common respiratory viruses • Upper respiratory tract infection includes • rhinitis (common cold), tonsillitis, pharyngitis • Lower respiratory tract infection includes • croup, bronchitis, bronchiolitis, pneumonia

4. ORTHOMYXOVIRIDAE • Orthomyxoviruses are spherical, enveloped viruses containing a segmented, negative strand RNA genome • Viruses in this family infect humans, horses, and pigs, and are the cause of influenza • Orthomyxoviruses are divided into three types: • Influenzae A, B, and C • Only influenza virus types A and B are of medical importance • Type A influenza viruses differ from type B viruses in that they have an animal reservoir and are divided into subtypes • Influenza virus C is not a significant human pathogen

5. Structure • Influenza virions are spherical, enveloped, pleomorphic particles • Two types of spikes project from the surface • One is composed of H protein and the second of N protein • Both the H and N influenza proteins are integral membrane proteins • The M (matrix) proteins underlie the viral lipid membrane • The RNA genome, located in a helical nucleocapsid, is composed of eight distinct segments of RNA • Each of which encodes one or more viral proteins • Each nucleocapsid segment contains not only the viral RNA but also four proteins

6. Influenza Virus • Orthomxoviridae family • They are helical, enveloped, single stranded RNA genome • They are enclosed in a lipid envelop and a layer of glycoprotein spikes • known as haemagglutinin (HA) and neuraminidase (NA), which are major antigenic determinants • They are divided into different genera on the basis of the nucleoprotein antigen • Genera A, B, C • Pathogenesis • The virus infects the epithelial cells of the nose, throat, bronchi and occasionally the lungs

7. Clinical Significance • Influenza spread by respiratory droplets and is an infection solely of the respiratory tract • There is rarely viremia or spread to other organ systems • Influenza has an acute onset, with symptoms including a nonproductive cough and chills, followed by high fever, muscle aches, and extreme drowsiness • Runny nose is unusual, differentiating influenza virus infection from the common cold • The disease runs its course in 4 to 5 days, after which recovery is gradual • The most serious problems, such as development of pneumonia or bacterial pneumonia

9. InfluenzaVirus Electron micrograph. Electron micrograph.

10. Influenzaviral proteins • Haemagglutinin (H) • Attachment to the cell surface receptors • Antibodies to the HA is responsible for immunity • 16 haemagglutinin antigenic type, H1 – H16 • Human associated H antigenic type are H1, H2, H3 • Neuraminidase (N) • Responsible for release of the progeny viral particles from the infected cell • 9 neuraminidase antigenic type, N1 – N9 • Human associated N antigenic type are N1, N2

11. Summary of the ecology of influenza viruses

12. Prevention • Influenza vaccine: Two types of vaccines available 1- The flu shot vaccine: Inactivated (killed vaccine) • Given to people older than 6-months, including healthy people and those with chronic medical conditions 2- The nasal spray flue vaccine: Live attenuated vaccine • Approved for use in healthy people between 5-49 years of age • Both vaccines contain two strains of the current circulating influenza A and B viruses • Vaccine should be given in October or November • before the influenza season begins

13. Role of H AND N Proteins • H = Hemagglutinin and N = Neuraminidase • Hemagglutininallows the virus to bind to host cells • Neuraminidasehelps the virus to release itself from the highjacked cells in which it has reproduced • Influenza A Virus Constantly Changes • Antigenic drift • Small changes in H or N proteins that occur from year to year • Population is partially immune, but may be re-infected over time (periodic epidemics) • Antigenic shift • Acquisition of new H or N protein, possibly from an animal virus • Population is not immune, everyone is susceptible (pandemics)

14. Influenza A Virus • Influenza A virus only is further classified into subtypes based upon HA and NA antigens • 16 HA subtypes and 9 NA subtypes are now recognized circulating in birds, humans, swine and horses • The most famous subtypes are: • A (H1N1): circulating in humans causing swine flu • A (H5N1): circulating in birds causing avian flu

15. Clinicalpicture • Fever • Headache • Myalgia • Cough • Rhinitis • Ocular Symptoms Incubation period: 1 to 2 days • Transmission: droplet infection or hand-to-hand contact • Diagnosis: • 1- Isolation of the virus from nose, throat swab • 2- Tissue culture • 3- Provisional - clinical picture + outbreak

16. Avianflu • Viral etiology: Avian influenza type A virus (H5N1) • Family: orthomyxovirus • Epidemiology • Wild birds are the natural reservoir for the virus • They shed the virus in saliva, nasal secretion and feces • All domestic poultry are susceptible to infection • They become infected, when they eat food contaminated with secretion from infected bird • Avian influenza viruses do not usually infect human • High risk group includes those who working in poultry farms and those who are in close contact with poultry

17. Symptoms in human • Ranges from typical flu to severe acute respiratory disease • Diarrhea, abdominal pain and bleeding from the nose have been reported • Treatment • Should be initiated within 48 hours • Lab diagnosis • PCR, detection of the viral RNA in throat swap

18. ParainfluenzaVirus • Family: Paramyxoviridae • Structural features • Enveloped virus with - ssRNA genome, with 5 serotypes • Transmission • Inhalation of infectious aerosol droplets mainly in winter • Clinical syndrome • Croup (or laryngotracheobronchitis) • Fever, harsh cough, difficult inspiration can lead to airway obstruction need hospitalization to do tracheostomy • Bronchiolitis and Pneumonia • Lab diagnosis • Direct detection immunofluorescence • Treatment and prevention • Supportive treatment, No specific treatment or vaccine available

19. Respiratory Syncytial Virus (RSV) • Family: Paramyxoviridae • Structural features: Enveloped virus with - ssRNA genome • Transmission: Inhalation of infectious aerosols mainly in winter • Clinical syndromes: • Bronchiolitis • Life-threatening disease in infant especially under 6 month of life with respiratory distress and cyanosis can be fatal and can lead to chronic lung disease in later life • Pneumonia • can also be fatal in infant

20. Lab diagnosis • Isolated of virus by cell culture • Direct detection of the Ag by direct I.F. • Treatment and prevention • Ribavirin administered by inhalation for infants with severe cases • Vaccine • No vaccine available, but passive immunization immunoglobulin can be given for infected premature infants

21. Rhinovirus • Family: Picornaviridae • Structural features: Non-enveloped virus with + ssRNA genome, more than 100 serotypes available • Transmission: Inhalation of infectious aerosol droplets • Clinical symptoms: The 1st cause of common cold. The main symptoms of common cold are sneezing, clear watery, nasal discharge with mild sore throat, and cough • Lab diagnosis: Direct detection of the Ag by direct I.F. • Treatment and prevention: Usually self-limiting disease, no specific treatment, and no vaccine available

22. Coronavirus • Family: Coronaviridae • Structural features: They are large helical, enveloped, single stranded RNA viruses • Transmission: Inhalation of infectious aerosol droplets • Clinical symptoms: The 2nd cause of common cold. The human coronaviruses (CoVs) are responsible for about 30% of mild upper respiratory tract illness (common cold) • Severe Acute Respiratory Syndrome (SARS) • Newly emerged SARS-CoV causes severe acute respiratory syndrome (SARS) that has been reported in Asia, North America, and Europe • In winter of 2002, a new respiratory disease known as (SARS) emerged in China • A new mutation of coronavirus MERS-CoV, with probably an animal reservoir, and cause atypical pneumonia with difficulty in breathing • Treatment and prevention: No specific treatment or vaccine available, yet

23. SARS Disease • Severe acute respiratory syndrome (SARS) • viral respiratory disease • zoonotic origin • caused by the SARS coronavirus (SARS-CoV) • Incubation period: 2 - 10 days • Transmission: droplet infection or contact to contaminated skin or fomites • Clinical Picture • Fever, chills, headache, myalgia and malaise • Respiratory symptoms often begin 3-7 days after symptom onset and peak in the second week • Laboratory Diagnosis • Serological Testing • IFA: Indirect fluorescent antibody • ELISA: Enzyme-linked immunosorbent assays • Molecular Testing • RT-PCR: Reverse transcriptase-PCR • Culture:SARS-CoV (Vero E6 cell)

24. Adenovirus • Family: Adenoviridae • Structural features: Non-enveloped virus with ds-DNA genome • Pathogenesis: Adenovirus infects epithelial cell lining respiratory tract, conjunctiva, urinary tract, gastrointestinal tract and genital tract. • Clinical syndrome • Phrayngitis and tonsilitis • Pharyngioconjunctivitis • Keratoconjunctivitis • Pneumonia: in preschool children • Gastroenteritis • Acute hemorrhagic cystitis • Cervicitis and urethritis • Treatment and prevention: No specific treatment or vaccine