1 RNA viruses pathogenic variants persistent infections Emerging viruses Antigenic variation Zoonotic disease

2 Orthomyxoviruses segmented RNA genomes – 8 segments; 14 kb 2 envelope glycoproteins - haemagglutinin and neuraminidase (key targets of humoral immune responses)  Influenza viruses cause serious respiratory and systemic disease in animals and man  Major antigenic shift may be associated with genetic reassortment between strains of virus ss RNA enveloped, helical nucleocapsid, pleomorphic 100nm myxo = mucus

3 Orthomyxovirus Structure  -ss RNA  matrix proteins  2 envelope glycoproteins  haemagglutinin (H or HA)  receptor binding  uncoating  neuraminidase (N or NA)  release  receptor binding

4 Orthomyxovirus Replication HA :sialic acid RNA synthesis - transcription - replication viral polymerase nucleus antiviral drugs applied in human medicine blocked by amantadine - target M2 blocked by Tamiflu - target neuraminidase virus assembly

5 Isavirus genus Infectious salmon anaemia Emerging disease in farmed salmon : 1984 (Norway) Scotland 1998/9 £20Million, eradicated important genera : Influenza A (avian/mammalian) Isavirus (fish) Veterinary Orthomyxoviruses

6  wild aquatic birds (waterfowl and shorebirds)– alimentary tract  infection largely asymptomatic  transmitted faecal/oral route (waterborne)  ALL H [16H types] and N [9N types] Influenza A : Reservoir - Influenza A viruses

7  infection of mammals usually restricted to respiratory tract  transmitted by aerosol  Limited H and N types Equine influenza - Swine influenza Fowl plague - NOTIFIABLE Human influenza [Theme - Zoonosis]

8 N1 N2 N3 N4 N5 N6 N7 N8 N9 H1 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 H2 Aquatic avian species - all H,N Man, pigs, horses limited H,N types H and N types in various species H16

9 Antigenic Shift Antigenic Drift spontaneous mutations in surface antigens  selection of variants in a partially immune population new strain H1 N1 H2 N2 circulating human influenza strain avian influenza strain Reassortment H2 N2 major change in surface antigenicity - associated with reassortment (or recombination)

10 Transmission of Influenza A wild/domestic birds man pigs known ?

11 Equine influenza  First isolated 1956  Two subtypes : H3N8, classical H7N7 Swine Influenza First observed 1918 U.S. during Spanish flu. Currently circulating strains are H1N1 (avian derived), and H3N2 and H1N2 (human-like reassortant strains)

12 Spanish flu [1918]  killed more people than 1st World War  high mortality rate  killed young and healthy Emergency hospital during influenza epidemic, Camp, Kansas

13 Highly Pathogenic AI (HPAI, Fowl Plague)  Pathogenic H5 and H7 strains of avian influenza virus  Affects turkeys, chickens with mortality up to 100%  NOTIFIABLE: Control : culling (affected farms + 3km radius), isolation of waste, restriction zones, disinfection of premises  In infections with the most virulent strains there is viraemia and multifocal lymphoid and visceral necrosis, leading to pancreatitis, myocarditis, myositis, and encephalitis.  Chickens and turkeys succumbing after several days of illness exhibit petechial hemorrhages and serous exudates in respiratory, digestive, and cardiac tissues.  Turkeys may also have air sacculitis and pulmonary congestion.

14 H5N1 spread: poultry & wild birds >200 million Poultry culled

15 Human influenza virus pandemics  exposure to influenza virus (of different antigenic type) circulating in another species [1] which can replicate and cause clinical disease in man [2] - transmission from pigs infected with human/animal/avian reassortants - adaptation of avian virus in pigs (or in humans) - direct transmission (e.g. birds to man) [re-emergence from environmental reservoir]  adaptation, drift, shift in new host [3] World-wide surveillance of influenza outbreaks in man/animals/birds : World Health Organisation Pandemic : virus must transmit efficiently between humans

16 Human Influenza Pandemics 1957 asian 1968 hong kong H1N1 no longer circulating H2N2 no longer circulating H1N1 H3N2 H1N spanish H1N1 [Avian] H1 N1 H2N2 [Avian] H2 N2 [Avian] H3 N2 H3N2 [1977] In current circulation

17 63% mortality rate by H5N1 in humans

18 CORONAVIRUSES corona = crown (latin) Helical nucleocapsid Membrane Spike Positive sense single stranded RNA Enveloped 120nm, positive sense ssRNA with helical nucleocapsid.

19 Key features 1. Associated mainly with enteric and respiratory diseases. The most important are infectious bronchitis of chickens and feline infectious peritonitis of cats. 2. The envelope glycoproteins as very conspicuous, petal-like structures called peplomers. The consequent distinctive crown (corona) -like structure gives the group its name. 3. Very prone to mutations affecting antigenicity and virulence. 4. Diagnosis: don’t generally grow in cell culture - therefore use serology, histopathology, RT-PCR

20 B & C: ADE, absorption requires only Fc receptor A: normal infection, attachment to cellular receptor Some FCoV vaccines have enhanced ADE (and disease) on challenge Immunne evasion

21 Coronaviruses CHICKEN DOG CAT HUMAN respiratory/urogenital intestine respiratory intestine/macrophages respiratory IBV FCoV HCV 229E HCV OC43 SARS CCoV CRCoV

22 Infectious bronchitis IBV is a commercially very important disease of both broilers and layers. The virus replicates in the respiratory and urogenital tracts. In chicks I to 4 weeks of age, virulent virus strains produce gasping, coughing, rales, nasal exudate, and respiratory distress. Young chicks may develop a severe tracheitis with a mortality rate of up to 90%. Chick layers that survive may have defects in the oviduct that prevent egg production in the adult bird. Primary infection of adult laying birds may not be associated with clinical signs but infection of the oviduct leads to a severe drop in egg production and the eggs are often misshapen and soft-shelled.

23 Canine coronaviruses Canine enteric CoV CECoV (CCoV) – types I, II Canine respiratory CoV (CRCoV) [group 2] - ‘discovered’ 2003 Involved in canine infectious respiratory disease with CHV, CAV-1, canine parainfluenza virus + other agents

24 Feline coronaviruses Biotypes FECV (FCoV) feline enteric coronavirus FIPV feline infectious peritonitis virus Genotypes type 1, type 2 Most infections are inapparent or result in mild diarrhoea. The virus normally grows in the intestinal tract and is shed in the faeces. Carrier cats are important in transmission. Occasionally an infected (seropositive) cat develops FIP

25 0 FCoV shedding in 70% of exposed cats Months 2d p.i d uninfected infected The main source of FCoV infection is contact with faeces or the used cat litter of infected cats. FCoV can survive up to 7 weeks in dried up cat litter. 15% cats become lifelong FCoV shedders

26 FCoV FIPV wet dry Replication in macrophages Immune complex formation in blood vessels Immune mediated vasculitis Mild/subclinical enteritis Pathogenesis of FIP Clinical forms FIP Effusive (wet) Non-effusive (dry)

Coronaviruses mutate/recombine easily giving rise to different biotypes FCoV I/CCoV II FCoV II FCoV FIPV ? Mutation within infected animal to generate pathogenic strain Theme: Emerging virus

28 SARS Severe acute respiratory syndrome : SARS-CoV asia –> spread to americas, europe 800 deaths Possible source : CoV of palm civet – from bat? man ~90% sequence identity