GOALS FOR THE VIROLOGY LECTURES Each lecture attempts to answer the following questions. What are the general characteri

1. GOALS FOR THE VIROLOGY LECTURES • Each lecture attempts to answer the following questions. • What are the general characteristics of this virus family? • What are some of the important viruses in this family? • What type of disease do the viruses cause? • Which animals does the virus infect? • Is the disease zoonotic? • What is the method of transmission of the virus? • What is the worldwide distribution of the viruses? – When and where should you be looking out for these diseases? • How do you diagnose the disease – differential diagnosis – Briefly • How is the disease controlled – Briefly.

2. Viruses with +ve RNA genomes foot and mouth disease virus Picornaviridae porcine enteroviruses Caliciviridae Coronaviridae feline calicivirus coronaviruses Arteriviridae equine arterivirus, PRRSV Flaviviridae flaviviruses (WNV) pestiviruses (BVD) Togaviridae equine encephalitis viruses

3. Caliciviridae The family consists of several viruses of veterinary importance including vesicular exanthema virus of swine, feline calicivirus, rabbit hemorrhagic disease virus, and European brown hare syndrome. Caliciviruses cause systemic diseases and gastroenteritis but some cause vesicular diseases.

4. General Characteristics of Caliciviridae • Small size 40 nm in diameter • Non-enveloped, nucleocapsid has icosahedral symmetry • Single molecule of linear single-stranded positive-sense RNA • Genome size 7.4 – 7.7 kilobases • Resistant to heat, detergent-based disinfectants, but rapidly inactivated by acidity (99% inactivation at pH = 3)

5. Images of Caliciviridae 3-D Structure of Calicivirus Capsid Negative EM stain Norwalk virus Norwalk virus

6. Classification • There are 4 genera, Vesivirus, Lagovirus, and 2 • unnamed genera. • Vesivirus –many genotypes. • Vesicular exanthema virus of swine – 13 genotypes • Sam Miguel virus of sea lions – 17 genotypes • Feline Calicivirus • Cetacean calicivirus (Tur-1) • Primate calicivirus (Pan-1) • Skunk calicivirus • Reptile calicivirus (Cro-1)

7. Lagovirus – 2 genotypes Rabbit hemorrhagic disease virus European brown hare syndrome Unnamed genus - SRSV group 2 viruses Toronto virus Lordsdale virus Several swine caliciviruses

8. Unnamed Second Genus • Contains human caliciviruses, including • - Sapporo virus • - Manchester virus • Unclassified caliciviruses • There are a number of unclassified caliciviruses, • including bovine enteric calicivirus, canine calicivirus, • mink calicivirus, porcine enteric calicivirus, walrus • calicivirus, lion calicivirus, chicken calicivirus.

9. VESICULAR EXANTHEMA VIRUS (VEV) -Vesivirus • VE disease of swine is extinct but the virus is still present • in marine mammals. • VE was an acute febrile disease of swine characterized • by formation of vesicles on the snout, teats, tongue, • oral cavity, and feet. • Disease important because it is indistinguishable • clinically with FMD, and VS.

10. VE Pathogenesis • Virus transmitted by contact and contamination of formites. • Incubation period was 18 to 48 hours. • Morbidity was very high. • Recovery was rapid with no complications. • Immunity was solid following infection but there were many non-cross-protective serotypes resulting in heterologous re-infections.

11. Clinical Disease • Fever, lameness, rapid weight loss. • Vesicles in snout, oral cavity, teats, and feet. • Mortality was low. • Virus causes encephalitis, myocarditis, diarrhea, and failure to thrive. • Pregnant sows may abort.

12. Vesicular exanthema snout showing ruptured vesicle

13. Vesicular exanthema tongue showing ulcerative lesions

14. Epidemiology and Control USA Policy that led to eradication Slaughter of all affected animals because of fear of FMD. Garbage feed to pigs was cooked. No vaccination was attempted.

15. Diagnosis • Virus isolation –in swine cell cultures • Serologic tests –Diff Diagnosis: FMDV, VSV • VE viruses were very heterogenous - 13 antigenic serotypes known. • Electron microscopy

16. FELINE CALICIVIRUS (FCV) - Vesivirus • Feline calicivirus disease is one of the two major • respiratory diseases in cats worldwide • FCV produces an acute or subacute disease characterized • by conjunctivitis, rhinitis, tracheitis, pneumonia, and • vesicular ulceration of the oral epithelium

17. FCV Pathogenesis • Natural transmission is via aerosol and formites - often transmitted to susceptible cats by human handlers. • Incubation period is 2 to 6 days. • Lesions are confined to respiratory tract, oral cavity, and eyes. • The virus is shed in large amounts from infected cats for months - persistent infection occurs in most animals, resulting in carriers. • Different strains of FCV vary in virulence. • Morbidity is very high.

18. Clinical disease • Fever, anorexia, lethargy, stiff gait, nasal and ocular discharges. • Conjunctivitis. • Ulcerative lesions are commonly observed in oral epithelium. • In severe disease, pulmonary edema and interstitial pneumonia. • Mortality can be as high as 30% in young kittens.

19. FCV Diagnosis • 1. Clinical presentation • 2. Virus isolation –feline cell cultures • 3. Serology – DD – Feline rhinotracheitis and feline herpesvirus-1

20. Epidemiology and Control • Disease is distributed worldwide. • Even though all Felidae species are susceptible, natural infections have only been reported in domestic cats and cheetahs. • The main control method is by vaccination -Attenuated and inactivated vaccines are widely used.

21. RABBIT HEMORRHAGIC DISEASE VIRUS Genus - Lagovirus Is a highly infectious disease of European rabbits first identified in China in 1984 It killed 470, 000 rabbits in the first 6 months in 1985 and rapidly spread throughout China

22. RHDV Pathogenesis • Infection is via fecal-oral route. Incubation period is short. • Lungs most severely affected with congestion and hemorrhage. • Splenomegaly and massive liver necrosis. Large blood clots in blood vessels indicative of disseminated intravascular coagulation.

23. Clinical disease • Disease occurs in rabbits over 2 months old. • Younger rabbits do not develop disease after infection. • Peracute disease - Fever, depression, sudden death within 6 to 24 hours. • Acute and subacute diseases – serosanguinous nasal discharges nervous signs. • Morbidity is 100% • Mortality rate is 90% in rabbits over 2 months old.

24. RHDV Diagnosis • NOTE: Virus has not been isolated in culture. • 1. Hemagglutination test – RHDV agglutinates • human erythrocytes • 2. Immunofluorescence Epidemiology and Control Inactivated homogenate vaccine available – with adjuvant Recent DNA vaccine developed but not available commercially.

25. RHDV as Biological Control • NOTE:In Australia and New Zealand rabbits number as • many as 100 million - cause an estimated $600 million • annual damage (loss of animal species, habitat and crop • destruction). • RHDV virus accidentally founds its way to the • Australian rabbits and served as an excellent biocontrol • agent. • Virus also accidentally introduced in New Zealand and • rabbit numbers dropped by up to 60% in some areas.

26. 19 August 2002 MINISTER KEMP'S ANSWERS ON RABBIT DISEASE FAIL TO SETTLE FRIGHTENING QUESTIONS Federal Minister for the Environment and Heritage, Dr David Kemp, has side-stepped several Questions on Notice posed by Senator Bob Brown about proposals to further spread the deadly haemorrhagic Rabbit Calicivirus Disease (RCD) in Australia. Animals Australia received copies of Dr Kemp's answers to 3 of the 4 questions, but the Minister has failed to give any assurance that a new bait delivery system for the disease is safe. After its mysterious first appearance in China in 1984, and its unexplained escape from Wardang Island (South Australia) in 1995, RCD was deliberately released by Governments across Australia in 1996 in the hope of reducing the wild rabbit population. The National Registration Authority is now considering a proposal to further spread the disease in Australia by placing the live virus on food baits. The Minister was asked if he is aware of a recent study that showed that pigs inoculated with the virus became sick. Senator Brown also asked the Minister to give a cast iron assurance that the disease will never spread to Australian pigs, or to any other species, including humans. Dr Kemp side-stepped this question - merely saying all decisions are based on a risk analysis. Executive Director of Animals Australia, Glenys Oogjes, said, "We are not surprised that the Minister is unable to give that assurance. The only scientists who have ever claimed that this virus - RCD - is safe for other species are those with a vested interest in covering up the risks - and even they have never said it will not cross species, only that cross-species infection is 'unlikely'. The new proposal for the disease to be put in baits (rather than injected into rabbits) will make it even more available to a broader range of animals. It is madness!" In 1996 Environment Australia (EA) gave the original proposal to release RCD infected rabbits into wild rabbit populations the thumbs up. A recent assessment report by EA of the current proposal to use virus baits has (again) concluded that the chances of cross-species infection are minimal.

27. Caliciviruses: 1 minute quiz • Please write responses to the questions on a piece of paper,add your name, date, and hand it in. • Caliciviruses only cause GIT infections. True or false • (2) Why has RHDV worked so well as biological control? • The calicivirus genome is almost the same size as that • of picornaviruses. True or False