Zika Virus. It may be devastating, But we might just get one step ahead of it. Learning in Retirement Winter 2017 Daniel Burnside. photo: Newsweek.

Transcription

1 Zika Virus It may be devastating, But we might just get one step ahead of it Learning in Retirement Winter 2017 Daniel Burnside photo: Newsweek.com

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3 INTRODUCTION TO VIRUSES STRUCTURE GENOME LIFE CYCLE

4 WHAT IS A VIRUS? Microscopic particles that infect other organisms and can only replicate within a host cell Contain either contain DNA or RNA surrounded by a protective structural viral coat or capsid Hijacks the biochemical machinery of the host, alters cell physiology, morphology, biochemistry etc.

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6 VIRUSES ARE TINY LITTLE THINGS nm

7 GENERAL STRUCTURE OF ANIMAL VIRUS 7 Copyright 2016 by Elsevier Inc. All rights reserved.

8 VIRAL MORPHOLOGY AND ASSEMBLY A highly-organized capsid comprised of proteins coded by the viral genome provides morphological distinction; - subunits called capsomeres spontaneously aggregate to form the capsid - spikes are glycoproteins which forms long projections out from the capsid and aid in viral attachment - some viruses have an envelope outside the capsid. Presence/absence classifies a virus as naked or enveloped - a fully assembled viral particle is known as a virion

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10 ENVELOPED VIRUS (CONT.) Might include some viral glycoproteins Some or all host membrane proteins are replaced by viral proteins Hemagglutinin (H) antigenic glycoprotein that helps virus bind to target cells Neuramadinase (N) cleaves sialic acid groups from host glycoproteins to encourage release from the cell Target of Tamiflu Influenza Virus 10

11 MULTIPLICATION OF ENVELOPED ANIMAL VIRUSES 11

12 LIFE CYCLE OF MAMMALIAN VIRUSES

13 VIRAL GENOMES REPLICATION AND TRANSLATION VARY GREATLY

14 ZIKV Photo: The Telegraph (UK)

15 ZIKA VIRUS THE HISTORY OF A DEVASTING VIRUS

16 ZIKA IS NOT A NEW VIRUS In 1947, scientists were screening for yellow fever in the Zika forest of Uganda and unintentionally isolate and document the Zika virus in a rhesus primate One year later, the virus is discovered in an Aedes mosquito 1952: Zika is first detected in humans in Uganda and Tanzania The virus spreads slowly across central Africa and into Asia including findings in India, Pakistan, Malaysia and Thailand Source: WHO International

17 ZIKA IS NOT A NEW VIRUS The first major human outbreak occurs in 2007 on the small island of Yap in Micronesia Prior to this outbreak, only 14 human cases had been reported worldwide (with only minor symptoms) , outbreaks occur throughout the Pacific Islands including a large outbreak in French Polynesia Source: WHO International March-April 2015 Brazilian public health officials document a viral outbreak affecting over 7000 individuals with an accompanying skin rash Zika not suspected or tested for February 2016 WHO declares a public health emergency as Zika is linked to a spat of cases of microcephaly and other associated neurological disorders

18 DETECTED IN 49 COUNTRIES

19 Slide courtesy NIH

20 ZIKA VIRUS: ON FEBRUARY 2 ND 2016, THE WHO DECLARED THE OUTBREAK A GLOBAL PUBLIC HEALTH EMERGENCY Member of the Flaviviridae family - Related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses Not highly contagious Transmitted by Aedes mosquitoes potentially through other varieties, also ticks etc. Symptoms are generally mild and last from days to a week; fever, rash, pain, conjuctivitis. Incubation is 3-12 days. Only 1 in 5 show symptoms. Women who are infected during pregnancy and highly likely to give birth to children suffering from microcephaly

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22 Slide courtesy NIH

23 THE SPREAD

24 ZIKA VIRUS: NOW WHAT? IN ALL HONESTLY, WE DON T KNOW THAT MUCH ABOUT IT (MY SLIDE FROM LAST YEAR) Examine thoroughly to check for link to microcephaly ( nearly done), ability to transmit in various species of mosquitos (in progress), mutations (not much yet ), epidemiology, effects on cellular physiology (in progress), vaccine development (done) Implement mechanisms of outbreak management (successfully implemented) Mechanism of microcephaly (maybe done???)

25 THE ZIKV GENOME 11 GENES, 1 POLYPROTEIN

26 MICROCEPHALY ALSO ENCEPHALITIS AND GUILLAIN BARRE SYNDROME

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28 FIGHTING BACK LET S KICK ITS ASS

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30 Case study of aborted fetus Found full ZIKV genome in the brain tissue Neurodevelopment appears aborted at ~20 weeks Two minor mutations, linked to Asian outbreak

31 case study of monogamous couple virus subsequently found in semen (other studies)

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34 Slide courtesy NIH

35 Slide courtesy NIH

36 MEANWHILE AT.

37 InSiPS is a genetic algorithm o Genetic algorithms mimic natural selection in silico o A starting population of sequences is evolved over multiple generations o A fitness function determines if sequences should advance to subsequent generations Selection and Mutation Selection and Mutation Select Optimal Solution Initial Population Final Population

38 Can we disrupt interactions between Zika proteins and human proteins to prevent the production of the virus and prevent side effects?

39 Designing protein-based drugs that can prevent the propagation of the Zika Virus

40 Credit: Tom Kazmirchuk

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