1 Structural Virology Lecture 10 Pavel Plevka © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 2 Lecture on 12.12. will take place in A35 - excursion to virology, cryo-EM and X-ray lab - demonstration of structural-biology approaches used in virology 3 Emerging viruses 4 Bunyaviridae Segmented -ssRNA linear genome, L segment is between 6.8 and 12 kb, M segment between 3.2 and 4.9 kb and S segment between 1 and 3 kb. Encodes for four to six proteins. 5 Paramyxoviridae -ssRNA ±15kB 6 Newcastle disease virus matrix protein © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 7 Newcastle disease virus – matrix protein © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 8 Newcastle disease virus © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 9 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 10 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 11 Paramyxoviridae - rubulavirus Mumps 12 Rubella – capsid protein structure © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 13 14 Flaviviridae © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 15 Flaviviridae - genome Flaviviruses  Tick-borne encephalitis  West Nile  Yellow fever  Dengue (strains 1-4) Mukhopadhyay et al. Science, 2003 I Yu et al. Science 2008 ? I Yu et al. Science 2008L Li et al. Science 2008 Dengue2 prR201A maturation mutant Furin cleavage site prR201A particles with “double” symmetry Correlation with model in orientation 1 Correlation with model in orientation 2 Combination of tomography and single particle data Structure of Dengue 2 maturation intermediate Correlation with immature model Correlation with low-pH immature model Relative orientations of immature and low-pH immature domains   3 32 5 26 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 27 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 28 Poxviridae © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 29 Coronaviridae © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 30 Coronaviridae © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 31 Learning outcomes • know the term ‘emerging virus’ • discuss examples of viruses that have recently appeared in new host species • discuss examples of viruses that have recently appeared in new parts of the world • discuss examples of new viruses • discuss examples of re-emerging viruses • assess measures that can be taken to prevent and contain outbreaks of infectious disease 32 Viruses and cancer © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 33 Papillomaviruses © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 34 Human Polyomaviruses Merkel cell carcinoma Mouse polyomavirus Progressive Multifocal Encephalopathy (JCV) MCV BKV JCV KIV WUV Inf. pop. (%) 42 82 39 55 69 SI to Mouse PyV 52 51 51 26 25 SI to SV40 48 81 76 26 27 Feng et al. Science, 2008; Koralnik. A Neur. 2006; Stehle et al. Nature, Li et al. Nature, 2003 Human Polyomaviruses Stehle et al. Nature, 1994 Liddington et al. Nature, 1991 37 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 38 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 39 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 40 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 41 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 42 Learning outcomes • outline the characteristics of viruses that are associated with cancers; • evaluate the evidence for association of viruses with some cancers; • discuss possible mechanisms for virus induction of cancer; • suggest how virus-induced cancers may be pre- vented. John B. Carter and Venetia A. Saunders © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 43 Figures Chapter 24 44 Bacteriophages © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 45 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 46 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 47 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 48 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 49 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 50 © 2012 John Wiley & Sons Ltd. www.wiley.com/college/carter 51