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What is a virus? Lecture 1 Biology W3310/4310 Virology Spring 2013 “There is an intrinsic simplicity of nature and the ul5mate contribu5on of science resides in the discovery of unifying and simplifying generaliza5ons, rather than in the descrip5on of isolated situa5ons in the visualiza5on of simple, overall pa<erns rather than in the analysis of patchworks” SALVADOR LURIA 1

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What  is  a  virus?Lecture  1

Biology  W3310/4310Virology

Spring  2013“There  is  an  intrinsic  simplicity  of  nature  and  the  ul5mate  contribu5on  of  science  resides  in  the  discovery  of  unifying  and  simplifying  generaliza5ons,  rather  than  in  the  descrip5on  of  isolated  situa5ons  -­‐  in  the  visualiza5on  of  simple,  overall  pa<erns  rather  than  in  the  analysis  of  patchworks”

-­‐-­‐SALVADOR  LURIA

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Biology  W3310/W4310Virology

• Prof.  Vincent  Racaniello,  Ph.D.

-­‐ [email protected]

-­‐ twiHer.com/@profvrr

-­‐ Google+  gplus.to/profvrr

• Prof.  Saul  Silverstein,  Ph.D.

-­‐ [email protected]

• TAs:  Ashlee  BenneH,  Stephanie  Sarbanes,  Katharina  Shaw

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Biology  W3310/4310Virology

• courseworks.columbia.edu

-­‐ Schedule,  readings,  screencasts,  grading

• virology.ws/course

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Biology  W3310/4310Virology

Textbook:  Principles  of  Virology,  Third  EdiUon,  ASM  Press

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Biology  W3310/4310Virology

• virology  blog:  www.virology.ws

• This  Week  in  Virology:  www.twiv.tv

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Biology  W3310/4310Virology

• Weekly  quiz

• 3  exams

• Discussion  sessions  (W4310  only)

• Extra  credit

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Biology  W3310/4310Virology

• Office  hours:  Thursdays  4-­‐6  PM,  HHSC  1310B,  701  W.  168th  (Medical  Center)

• Skype:  profvrr

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We  live  and  prosper  in  a  literal  cloud  of  viruses

• Viruses  infect  all  living  things  

• We  eat  and  breathe  billions  of  virions  regularly

• We  carry  viral  genomes  as  part  of  our  own  geneUc  material

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More  than  1030  bacteriophage  parUcles  in  the  world’s  waters!  

•  A  bacteriophage  par2cle  weighs  about  a  femtogram  (10-­‐15  grams)

1030  X  10-­‐15=  the  biomass  on  the  planet  of  BACTERIAL  VIRUSES  ALONE  exceeds  the  biomass  of  elephants  by  more  than  1000-­‐fold!

•The  length  of  a  head  to  tail  line  of  1030  phages  is  more  than  200  million  light  years!

hBp://www.phagehunter.org/2008/09/how-­‐far-­‐do-­‐those-­‐phages-­‐stretch.html

The  number  of  viruses  on  Earth  is  staggering

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Andromeda  Galaxy  -­‐  2.5  million  light  years  away

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There  are  ~1016  HIV  genomeson  the  planet  today

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How  ‘infected’  are  we?

• HSV-­‐1,  HSV-­‐2,  VZV,  HCMVEBV,  HHV-­‐6,  HHV-­‐7,  HHV-­‐8

• Once  infected,  it  is  for  life

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You  are  a  reservoir  for  viruses  that  have  set  up  residence  in  your  lungs,  gastrointesJnal  tract  

and  other  places

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Amazingly,  the  vast  majority  of  the  viruses  that  infect  us  have  liNle  or  no  impact  on  our  health  or  well  

being

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Not  all  viruses  make  you  sick...

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The  good  viruses

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Viruses  are  amazing

This  course  will  teach  you  why  and  how

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•This  course  is  designed  to  help  you  see  the  ‘big  picture’  of  virology

•I’ll  show  you  how  to  think  about  virology  as  an  integraUve  discipline,  not  an  isolated  collecUon  of  viruses,  diseases,  or  genes

•You  will  learn  the  fundamentals  about  these  molecular  wizards  that  amaze  the  informed  and  frighten  the  uninformed

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What  is  a  virus?

• An  infec5ous,  obligate  intracellular  parasite

• Package  genome  in  a  parUcle  for  transmission  from  host  to  host

• Viral  genome  contains  informaUon  to  iniUate  and  complete  an  infecUous  cycle  within  a  cell

• All  viral  genomes  are  able  to  establish  themselves  in  a  host  populaUon  so  that  viral  survival  is  ensured

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Are  viruses  alive?

hHp://www.virology.ws/are-­‐viruses-­‐alive/

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The  virus  and  the  virion

A  virus  is  an  organism  with  two  phases

virion infected  cell32

As  virions  are  obligate  molecular  parasites,  every  soluUon  must  reveal  something  about  the  host  as  well  as  the  virus

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Be  careful:  Avoid  anthropomorphic  analyses

Viruses  do  NOT  think!(or  employ,  ensure,  exhibit,  display,  etc...)

They  do  not  achieve  their  goals  in  a  human-­‐centered  manner

They  survive  because  they  make  huge  numbers  of  mutants,  and  selecUon  removes  the  ill-­‐adapted

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E.  coli

Carbon  atom

myosin ac2n

Viruses  are  very  small

100,000x

1,000,000x

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How  many  viruses  can  fit  on  the  head  of  a  pin?

• 500  million  rhinoviruses

• When  you  sneeze,  you  fire  an  aerosol  that  contains  enough  viruses  to  infect  thousands

2  mm  =  2000  microns

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Mimivirus  parJcles  can  be  seen  bylight  microscopy

giantvirus.org38

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Viruses  replicate  by  assembly  of  pre-­‐formed  components  into  many  

parJcles

Not  binary  fission  like  cells  

Make  the  parts,assemble  the  final  product

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• EsUmates  of  molecular  evoluUon  place  some  viruses  among  the  dinosaurs

• Likely  evolved  much  earlier

How  old  are  viruses?

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Ancient  references  to  viral  diseases

1580-­‐1350  B.C.700  B.C.

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• PrevenUon  of  virus  infecUons  in  pracUce  since  the  11th  century  without  knowledge  of  agent

• Survivors  of  smallpox  protected  against  disease

• Variola5on  -­‐  inoculaUon  of  healthy  individuals  with  material  from  a  smallpox  pustule  (Lady  Montagu)

• 1790s  -­‐  experiments  by  Edward  Jenner  in  England  establish  vaccinaJon

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Concept  of  microorganisms

• Leeuwenhoek  (1632  -­‐  1723)

• Pasteur  (1822  -­‐  1895)  

• Koch  (1843-­‐1910)

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Virus  discovery  -­‐  filterable  agents

• 1892  -­‐  Ivanovsky

• 1898  -­‐  Beijerinck:  contagium  vivum  fluidum

• virus:  slimy  liquid,  poison

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Virus  discovery

• 1898  -­‐  Loeffler  &  Frosch  -­‐  agent  of  foot  &  mouth  disease  is  filterable

• Key  concept:  agents  not  only  small,  but  replicate  only  in  the  host,  not  in  broth

• 0.2  micron  filters  (µm,  one  millionth  of  a  meter)

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Virus  discovery

• 1901  -­‐  first  human  virus,  yellow  fever  virus

• 1903  -­‐  rabies  virus

• 1906  -­‐  variola  virus

• 1908  -­‐  chicken  leukemia  virus,  poliovirus

• 1911  -­‐  Rous  sarcoma  virus

• 1915  -­‐  bacteriophages

• 1933  -­‐  influenza  virus48

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We  know  many  details  about  viruses

Chemical  formula  for  poliovirus:  C332,652  H492,388    N98,245  O131,196    P7,501    S2,340  

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Virus  classificaJon

• Nature  and  sequence  of  nucleic  acid  in  virion

• Symmetry  of  protein  shell  (capsid)

• Presence  or  absence  of  lipid  membrane  (envelope)

• Dimensions  of  virion  &  capsid

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Virus  classificaJon

Classical  hierarchical  system:

Kingdom

Phylum

Class

Order  (-­‐virales)

Family  (-­‐viridae)

Genus  (-­‐virus)

Species

Filoviridae  (filovirus  family)

Ebolavirus

Zaire  ebolavirus

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• 40,000  virus  isolates  from  bacteria,  plants,  animals  placed  in  6  orders,  87  families,  349  genera,  2284  species.

• BUT  -­‐  there  are  1030  virions  in  the  oceans!

hHp://ictvonline.org/

ICTV

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Analyzed  DNA  from  Lake  Limnopolar,  AntarcUca.  Found  10,000  species,    from  12  different  families,  

some  completely  new.

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Raw  sewage  harbors  diverse  viral  populaJons

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There  is  an  underlying  simplicity  and  order  to  viruses  because  of  two  simple  

facts

• All  viral  genomes  are  obligate  molecular  parasites  that  can  only  funcUon  aser  they  replicate  in  a  cell

• All  viruses  must  make  mRNA  that  can  be  translated  by  host  ribosomes:  they  are  all  parasites  of  the  host  protein  synthesis  machinery

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