Lecture 32 Emerging viruses

1. Lecture 32 Emerging viruses Definition: viruses that are in the process of adapting to a new host and vice versa. Though emerging viruses tend to be at first highly virulent, virus and host co-evolutionary processes tend to converge to less virulent virus and more resistant host populations. Examples of emerging viruses Myxoma virus (Rabbitpox) Influenza and Coronaviruses are constantly emerging

2. Myxomatosis: a classic tale of an emerging virus • For more info, go to: http://www.burrill.demon.co.uk/meddoc/myxo.html

3. Background • In 1759, the European wild rabbit O. cuniculus was introduced into Australia by Thomas Austin for sport hunting. Almost all of the rabbits in Australia are descendants of the 24 original rabbits. • The rabbit spread rapidly, at a rate of advance of about 110 kilometres each year. It now occurs over half of Australia. • The lack of any herbivores capable of competing with the rabbit resulted in the decline of many species of native wildlife by competing with them for food or burrows. This applies particularly to the small ground-dwelling mammals of the arid lands. This situation was made worse by the lack of a large population of predators able to deal with this new prey. • By the mid-20th century, rabbits had denuded the landscape • They couldn’t be eradicated by hunting or poisoning • Something else had to be done

4. Myxomavirus • Myxoma virus, a member of the large Poxvirus group about 280nm in length. • Myxomtosis: The disease was uncovered in South America in 1896 where it had devastating effect on the rabbit population there. • It was found that it was mainly the European rabbit (Oryctolagus cuniculus), imported early that century, that contracted the disease. • Myxoma virus is endemic to the local wild rabbit population (Sylvilagus brasiliensis) which was mostly resistant to the disease and acted at the natural reservoir. • The disease is highly lethal to European rabbits with observed mortality rates of greater than 99%. • Myxoma virus is transmitted by • Contact infection – Discharge from skin and ocular lesions. • Arthropod vectors – Mosquitos, fleas, mites, ticks. Myxoma virus particles

5. The Plan • 1919: first suggestion to use Myxoma virus to control rabbits in Australia. • 1950: Myxomatosis successfully released among Australian rabbits. • Initial mortality rates >90%. • Best spread by mosquitoes in summer. • Epidemic continued for 4 or so years with high mortality rates

6. The outcome – a paradigm of host/virus co-evolution • The virus: • highly virulent forms killed hosts too quickly to be effectively spread • Less virulent forms didn’t kill hosts, more virus produced over longer time • Selection for attenuated virus. • The host: • Susceptible hosts were quickly culled from the population • More resistant hosts lived to reproduce •  Selection for resistant rabbits. • Today: myxomatosis in Australia kills only about 40% of infected rabbits, but rabbit numbers are much lower than they would be in the absence of this disease.

7. Myxomatosis in Europe • Similar to Australia, rabbits were a major cause of damage, particularly to the national forests of France. • 1952: Dr P.F. Armand Delille inoculated two wild rabbits at Maillebois in northern France. • From these two rabbits myxomatosis spread all round Europe, including Britain and Ireland, and as far a field as North Africa. • The main means of transmission of the virus was the mosquito as well as the rabbit flea. • The disease had the same result as in Australia: the majority of the wild rabbit population of Europe was wiped out, including an estimated 90% of French and British rabbits.

8. Myxomatosis in Europe • Attenuation and genetic resistance has occurred in Europe • Unlike in Australia where the highly attenuated strains have replaced the virulent original, in Europe the two coexist. • This is due to a different vector situation where the rabbit flea is believed to be the main vector, especially in Britain where the variation in number of cases of myxomatosis does not vary greatly throughout the year. • Myxomatosis is now an enzootic disease in the wild rabbits of Europe, with occasional summer epizootics, particularly in France.

9. Constantly emerging viruses • Influenza • Coronaviruses.

10. Influenza • All aspects of Influenza A conspire for it to be a constantly emerging virus • Genome: 9 segments of (+) strand RNA. • Segments: Allows for large scale recombinationv – genetic shift. • RNA genome: RDRPs have high error rates…high rates of mutation – genetic drift. • Ecology: reservoir is migrating waterfowl. Alternate hosts are almost all mammals. Impossible to eradicate. • Anthropology: Crowded, agrarian culture in Southeast China provides the ideal environment for exchange of virus variants between hosts. • Technology: high mobility of post 18th century humans ensures efficient and rapid dissemination of new virus variants.

11. The result • Yearly epidemics due to genetic drift. • Virus and host populations evolve toward benign relationship • Periodic pandemics due to genetic shift • Highly virulent virus released on an immunologically naïve population • Both host and virus co-selected • And the cycle continues

12. Control • The WHO monitors Influenza subtypes in Southeast Asia • They have to “guess” which ones will become the most prevalent • Use these to design the vaccine for 2 years later. • It is a hit or miss process.

13. Coronaviruses. • For more information, see http://www-micro.msb.le.ac.uk/3035/Coronaviruses.html • Human CoV cause ≈ 30% of common colds. • Other animal coronaviruses can cause more pathogenic disease, e.g. • Porcine Epidemic Diarrhea Virus • Mouse Heptitis Virus • Avian Infectious Bronchitis virus • SARS-CoV: a scary emerging virus.

14. SARS-CoV • SARS is a type of viral pneumonia • Symptoms include fever, dry cough, dyspnea (shortness of breath), headache, and hypoxaemia (low blood oxygen concentration). • Typical laboratory findings include lymphopaenia (reduced lymphocyte numbers) and mildly elevated aminotransferase levels (indicating liver damage). • Death may result from progressive respiratory failure due to alveolar damage. • The typical clinical course of SARS involves an improvement in symptoms during the first week of infection, followed by a worsening during the second week. • Studies indicate that this worsening may be related to patient's immune responses rather than uncontrolled viral replication. • The SARS virus is believed to be spread by droplets produced by coughing and sneezing, but other routes of infection may also be involved, such as faecal contamination, so wash your hands!

15. History • Severe Acute Respiratory Syndrome (SARS) first appeared in Guangdong Province, China late in 2002. • Its rapid transmission and high rates of mortality and morbidity resulted in a significant threat to global health by the spring of 2003, and the epidemic had significant impacts on the public health and economies of locales affected by SARS outbreaks. • The rapid response of the World Health Organization is credited with containing this contagion by late June of 2003, and only a few cases were reported during the winter cold season of 2003-2004.

16. History The severity of this crisis mobilized the scientific community as well: by March 24, 2003, scientists at the CDC and in Hong Kong had announced that a new coronavirus had been isolated from patients with SARS. • The sequences from two isolates of SARS CoV were published simultaneously on May 1, 2003.

17. Organization of the SARS-CoV genome SARS-CoV Viral Particle Evolutionarily, SARS-CoV is in a class by itself

18. Origins (Good eatin’) • Coronaviruses with 99% sequence similarity to the surface spike protein of human SARS isolates have been isolated in Guangdong, China, from apparently healthy masked palm civets (Paguma larvata), a cat-like mammal closely related to the mongoose. • The palm civet is regarded as a delicacy in Guangdong • It is believed that humans became infected as they raised and slaughtered the animals rather than by consumption of infected meat.

19. Outlook • Could SARS coronavirus recombine with other human coronaviruses to produce an even more deadly virus? • Fortunately, the coronaviruses of which we are aware indicate that recombination has not occurred between viruses of different groups, only within a group, so recombination does not seem likely given the distance between the SARS virus and HCoV. • There is considerable experience of development of coronavirus vaccines for veterinary purposes – though not all of it is encouraging. • On the whole, inactivated coronavirus vaccines induce poor protection.

20. Outlook • The spike protein alone can induce immunity, but the internal nucleoprotein has also been reported to induce protective immunity. • The WHO has recommended that SARS vaccines be developed. • The quickest and probably safest to develop would be an inactivated or subunit vaccine. • Even if such a vaccine were not fully protective against SARS infection, it might still provide some protection against life-threatening SARS pneumonia.