BBS2711 Virology RESPIRATORY VIRUSES. Dr Paul Young, Department of Microbiology & Parasitology. Respiratory Viruses

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1 BBS2711 Virology RESPIRATORY VIRUSES Dr Paul Young, Department of Microbiology & Parasitology. Respiratory Viruses Respiratory tract is major route of invasion for a wide range of viruses LOCAL Vs SYSTEMIC SPREAD Viruses producing LOCAL respiratory sysmptoms Orthomyxoviruses Paramyxoviruses Picornaviruses Coronaviruses Adenoviruses Herpesviruses Influenza Parainfluenza, Respiratory Syncytial virus Rhinoviruses, some enteros Most species Most species EB virus, herpes simplex, CMV 1

2 Respiratory Viruses Respiratory tract is major route of invasion for a wide range of viruses LOCAL Vs SYSTEMIC SPREAD Viruses producing GENERALIZED disease - systemic spread Paramyxoviruses Togaviruses Herpesviruses Picornaviruses Bunyaviruses Mumps, measles Rubella Varicella (Chicken pox) Some enteroviruses Hantaan virus Major problem clinically primarily because of frequency - high infection/disease Most respiratory viruses can infect any level of the RT although preferred sites exist - eg rhinoviruses in URT 2

3 Transmission usually by droplet infection in aerosols size of droplet crucial to successful transmission - optimal around 5 µm also influences site of localization larger trapped in nasal baffles smaller carried into lungs variation in abilities to transmit based on virus and nasal secretion production Common cold - >50% caused by rhinoviruses and coronaviruses 3

4 Common cold - >50% caused by rhinoviruses and coronaviruses Common cold - >50% caused by rhinoviruses and coronaviruses 4

5 Otitis media Auditory (eustachian) tube many viruses capable of invading air spaces associated with URT (middle ear, sinuses) problem arises with secondary bacterial invaders (Strep. Pneumoniae, H. influenza) studies have shown >60% attacks originate with viral infection - particularly RSV fluid often persists in middle ear for weeks or months ( glue ear ) - can contribute to hearing impairment and learning difficulties. Influenza viruses members of the Orthomyxoviridae ("myxo" = affinity for mucins) - three types (based on antigenicity of NP) A - principal cause of epidemic influenza also infects animals (birds, pigs, horses) B - milder disease - no animal reservoir C - rarely pathogenic for man - no animal reservoir 5

6 HEMAGGLUTININ NEURAMINIDASE MATRIX PROTEIN LIPID BILAYER POLYMERASE NUCLEOPROTEIN RNA nm diameter particle SS -ve sense RNA genome - 8 segments coding for 7 structural and 3 non-structural proteins nucleoprotein (NP) associated with RNA - helical structure + 3 polymerase proteins surrounded by matrix (M) protein surface membrane containing 2 projections, hemagglutinin (HA) and neuraminidase (NA) acute RTI usually occurs in epidemics also one of the great pandemic diseases world-wide pandemics due to emergence of new antigenic strains population has no pre-existing immunity in winter of 1918/ million people died New antigenic strains of influenza A emerge via 2 mechanisms Shift - arising through genetic recombination (reassortment) Mixed infection allows exchange of viral segments coding for either the H or N glycoproteins (possible animal origin) New types emerge every years allowing escape from herd immunity 6

7 1. Reassortment of the H and N genes between human and avian influenza viruses through a third host 2. Recycling of pre-existing strains 3. Gradual adaptation of avian influenza viruses to human transmission Drift - arising through spontaneous mutation in the H gene selection of mutants that escape immune surveillance gradual but continuous change (currently seen in H3) 7

8 Clinical features inhalation of infected secretions results in infection of and growth in superficial epithelium of both URT and LRT damage to cilia and desquamation 1-3 day incubation with 2-4 day clinical course high fever (interleukin-1 from macrophages) malaise, generalized aches (interferon) non-productive hacking cough Rarely: Primary pneumonia -sudden deterioration, onset of resp. distress and circulatory collapse -invariably fatal Secondary bacterial pneumonia -invasion of lungs by opportunistic bacteria; Staph, H.influenzae. High mortality but less than primary. Control Amantadine and Rimantadine Relenza drugs for systemic use; block virus penetration targets M2 (fusion inhibitor) effective in prophylaxis for high-risk individuals mild CNS side-effects used as outbreak control measure emergence of drug-resistant viruses necessitates short-term treatment, 3-5 days aerosolised drug for topical use; block virus escape (NA inhibitor) Current vaccine is combination of 3 strains grown in eggs and inactivated Influenza A, H1N1 and H3N2 Influenza B, 1988 strain these in subunit form also available ('split vaccines') all give 60-90% protection (for about 1 year) - new vaccine can be generated from currently circulating strains by reassortment 8

9 Respiratory Syncytial Virus Member of Paramyxoviridae (pneumovirus) -ve sense ss RNA genome cold most common manifestation of infection in infants may invade LRT and lead to bronchiolitis and pneumonia probably as result of restriction of the bronchiolar lumen following inflammation highest incidence in infants of all virus respiratory infections resulting in hospitalization most infections restricted to URT - LRT involvement in about 25% of cases up to 3% of all children born each year require hospitalization nosocomial spread a problem annual winter epidemics (summer in tropics) two serotypes (A & B) identified - variation within these groupings RSV sub-type A more often associated with severe disease reinfection common RSV diagnosis by virus isolation or direct IF on nasopharyngeal aspirates ELISA tests now available (RT-PCR in development) aspirated ribavirin appears to be an effective therapeutic 9

10 Rhinoviruses members of the Picornaviridae +sense ss RNA genome major cause of common cold mildly febrile in about 50% of infections attack rate is approx. 0.7 infections per person per year greater than 100 serotypes recognized changing pattern in community with developing immunity cellular receptor for Rhinoviruses identified - ICAM-1 target for anti-viral drug development 10

11 Learning objectives Distinction between viruses that remain localized with those that spread systemically Infection consequences at the surface of the respiratory tract Clinical outcome and details of selected respiratory pathogens 11