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1. Website for the IMIN message board: http://www.biology.ualberta.ca/courses/imin200 User ID:imin200 Password influ3nz@ Virology TA-Alysson Blaine blaine@ualberta.ca

2. Lecture 11/12. Emerging pathogens. • Most emerging pathogens are Zoonotic diseases • Zoonoses: HIV from primates • Evolution of +strand RNA viruses • Zoonoses: West Nile Virus from birds • Zoonoses: SARS from bats • Zoonoses: influenza • Spanish Flu H1N1 • Avian flu H5N1 • H1N1 or ‘swine flu’

3. Zoonosis: transfer of a pathogen from non-human animals to humans and subsequent spread of the pathogen between humans. 1959 HIV 1999 West Nile Virus in N. America 1997 H5N1 2003 SARS 2008-2009 H1N1 pandemic 2012 Novel Coronavirus

4. Zoonoses: HIV from primates Phylogenetic relationships of retroviruses show origin of HIV from primates. Sooty mangabey chimpanzee Equine infectious anemia Bovine immunodeficiency Feline immunodeficiency virus Phylogenetic tree of nucleotide sequences of pol gene. HIV-1 causes most disease. It resembles chimpanzee virus. HIV-2 also causes AIDs. Not as prevalent as HIV-1.

5. Animal origins of infectious disease: HIV from primates Congo 1959 index case Cameroon 1998 Phylogenetic analyses of HIV suggests that HIV jumped from primates more than once. Human serum sample taken in 1959 in the Congo was shown to be HIV-positive. Viral genome resembled the SIV genome that causes little disease in chimpanzees.

6. Many +strand RNA viruses are evolutionarily related. They shuttle between humans and birds Rhino/Polio Helicase-purple Genome linked protein -orange SARS Protease-red Protease-brown Polymerase-yellow Structural proteins not shown West Nile virus Figure 20.3 Virology Genomic differences place estimated divergence times at 4000 years.

7. Zoonosis: West Nile Virus Number of people infected with West Nile virus in US Fears of contaminated blood Canada ~400 cases ~10 cases in 2010 Since July 2003, testing in place. Symptomatic individuals only Endemic in Africa. Index case was probably an infected individual from Israel to New York in 1999. Spread across North America.

8. WNV symptoms may or may not be present-and may be severe Infection with WNV can be asymptomtic (no symptoms), or can lead to West Nile fever or severe West Nile disease. 20% of people who become infected with WNV will develop West Nile fever. Symptoms include fever, headache, tiredness, and body aches, occasionally with a skin rash and swollen lymph glands. While the illness can be as short as a few days, even healthy people have reported being sick for several weeks. The symptoms of severe disease (also called neuroinvasive disease, such as West Nile encephalitis or meningitis or West Nile poliomyelitis) include headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. 1 in 150 persons infected with WNV will develop severe disease

9. Host-virus relationship for West Nile virus 108 virus/ml Birds are natural host 103-105 virus/ml 400 virus/ml Staggering, Paralysis, 40% die Usually no symptoms, or fever, rash, vomiting, paralysis Humans and horses are dead end hosts because viral titre is not high enough to transmit from us to other animals. Vaccine for horses is available-recombinant protein Vaccines for humans are entering Phase 1 clinical trials.

10. The global SARS outbreak of 2003: * 8,098 probable cases and 774 deaths from SARS worldwide * 438 probable or suspected SARS cases, causing 44 deaths in Canada SARS: Severe acute respiratory syndrome Incubation period: 2-12 days Symptoms: fever, muscle soreness, dry unproductive cough, hypoxemia, and in some cases diarrhea

11. Epidemiological case study: Canadian SARS outbreak. Patients were in close contact Patient 1 visited Hong Kong and stayed at Hotel M. Transmission is through droplets or contact. Some individuals were ‘super-infective’ Symptoms include fever greater than 38oC, severe respiratory distress-generally takes up to 10 days to present. Individuals are not contagious until symptoms apparent.

12. Coronavirus Suspect in Global SARS Outbreak New strain of coronavirus called SARS-CoV was identified in many infected patients. Genome is ~30kb +strand RNA virus. Enveloped virus named for the crown of viral glycoproteins. Coronaviruses infect a wide variety of mammals and birds How can you prove which virus is the infectious agent?

13. Zoonosis: SARS Civet cats carry a coronavirus almost identical to SARS-CoV. SARS-CoV has a 29bp deletion. May 2003 Professor Yuen Kwok-yung of the University of Hong Kong microbiology department reported that the SARS virus may have jumped to humans from civet cats. The civet cat is considered a delicacy in southern China. Feb 2, 2004 four new cases of SARS- one a restaurant waitress serving wild game Recent evidence suggests that virus is evolving in civet cats at similar rate as in humans. This suggests that they are not the host.

14. SARS coronaviruses have been found in horseshoe bats. Three communal,cave-dwelling species from the genus Rhinolophus (horseshoebats) demonstrated a high SARS-CoVantibody prevalence: 13 out of 46 bats (28%) in R. pearsonifrom Guangxi, 2 out of 6 bats (33%) in R. pussilus from Guangxi, and 5 out of 7 bats (71%) in R. macrotis from Hubei. The highseroprevalence and wide distribution of seropositive bats isexpected for a wildlife reservoir host for a pathogen What links bats to emerging infectious diseases? Bats.pdf

16. Negative strand viruses always package the RNA-dependent RNA polymerase in infectious particles Measles influenza transcription replication Figure 6.1 Virology RNA-dependent RNA polymerases does both transcription and replication. What if you remove this protein from the virion?

17. Zoonosis: influenza Influenza viruses are named for their HA and NA types HA-hemagglutinin NA-neuraminidase. Humans infected with H1, H2, H3 strains. Three pandemics in history- 1918,1957, 1968,….. 2009. Seasonal influenza-H1N1 1997, 2004 and ongoing occasional cases-H5N1 avian influenza 2009 Pandemic influenza-H1N1 Box 15.2 Virology Phylogenetic evidence suggests that the 1918 “Spanish” flu came directly from birds. The “Asian flu” acquired 3 new genes from ducks. The Hong Kong flu acquired 2 more.

18. 1. Spanish Flu History 1918 Influenza: the Mother of All Pandemics Jeffery K. Taubenberger* and David M. Morens† *Armed Forces Institute of Pathology, Rockville, Maryland, USA; and † National Institutes of Health, Bethesda, Maryland, USA 1918 influenza killed young people. "U-" and "W-" shaped combined influenza and pneumonia mortality, by age at death, per 100,000 persons in each age group, United States, 1911–1918.

19. Recovery of the H1N1 1918 influenza virus from Alaska. Johan Hultin identified the Brevig mission as the site of deaths of 72 individuals in 1918 Brevig Mission. The graves of victims of the 1918 influenza 1997 Hultin returned to Brevig Mission and re-opened the grave. Jeff Taubenberger has reconstructed the 1918 virus. It is 100x more lethal to mice than other influenza strains.

20. 2. Avian Flu March 7, 2003 An Avian Flu Jumps to People H5N1 Most closely related to H5N1 from 1997 Hong Kong avian flu that infected 18 individuals-killed 6 H5N1 virus is deadly to poultry and humans. Humans that died were directly in contact with chickens.

21. Highly virulent H5N1 HK97 influenza encodes an NS1 variant that shuts down the interferon response. The NS1 gene of the virus differs from the non-pathogenic strain by one amino acid.

22. H5N1 has spread across most of Asia and parts of Europe. H5N1 is highly lethal in humans and birds. Dead crows at same farm. H5N1 Bird flu in Japan Many Asian countries are battling H5N1 Avian flu. 100s of Millions of chickens have been culled. Humans in close contact with birds have been killed. Limited evidence of human-human transmission.

23. Avian influenza kills tigers and leopards. Animals fed H5N1-infected chickens contracted avian influenza. Animals were becoming sick even after food source was changed, suggesting the virus could transmit between cats.

24. http://www7.nationalgeographic.com/ngm/0510/feature1/index.htmlhttp://www7.nationalgeographic.com/ngm/0510/feature1/index.html Robert Webster of St. Jude Children's Research Hospital in Memphis has studied flu viruses for 40 years and has never seen the likes of this one. "This virus right from scratch is probably the worst influenza virus, in terms of being highly pathogenic, that I've ever seen or worked with," Webster says. Not only is it frighteningly lethal to chickens, which can die within hours of exposure, swollen and hemorrhaging, but it kills mammals from lab mice to tigers with similar efficiency. Here and there people have come down with it too. Half the known cases have died.

26. 2009 flu pandemic in Canada From Wikipedia, the free encyclopedia an infected Alberta farm worker recently returned from Mexico had apparently passed the virus to a swine herd in his care.. Transmission from the same herd of pigs back to humans was revealed on 20 July, though it occurred on 7 May when the humans, health inspectors, were taking samples from the infected herd with improper self-protective measures.

28. Influenza update Feb 2013

29. http://www.virology.ws/ Additional courses in virology at U. Alberta IMIN 324 Introductory Virology BIOC 450 Mammalian Viruses BIOL 495 Zoonoses IMIN415 Mechanisms of Pathogenicity