The

 Science  of  Virology  

MCB 102 General Virology

  Expected  Learning  Outcomes    
 

•  define  the  term  “virus”  

•  enumerate   proper3es   of   viruses   and   explain   how  

viruses  differ  from  living    things  

•  discuss  reasons  for  studying  viruses  

•  iden3fy   important   scien3sts   and   their   significant  

contribu3ons   in   the   development   of   Virology   as   a  
Science  
What  is  VIROLOGY?  

study  of  viruses  and  

virus-­‐like  agents  
WHY  study  viruses?  

•   agents  of  diseases  

•  tools  for  inves3ga3ng  cellular  &  

molecular  biology  of  the  host  

•  important  role  in  evolu3on  

http://upload.wikimedia.org/wikipedia/
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 What  is  a  virus?  

•  viruses  are   a  form  of  life  

•  viruses  are  organic  structures  

that  interact  with  living  
organisms  

•  organisms  at  the  edge  of  life

Like  other  organisms,    
•  viruses  possess  genes  
•  evolve  by  natural  selec3on  
•  reproduce  by  crea3ng  mul3ple  copies    
 
 
Unlike  other  life  forms,  
Ø  viruses  do  not  have  cellular  structure  
Ø  do  not  have  their  own  metabolism  
Ø  cannot  naturally  reproduce  outside  a  host  
cell  
General  ProperGes  

•  obligate  intracellular  parasites  

•  acellular  organizaGon  &  paKern  of        
reproducGon  
•  protein  coat  (capsid)  +  geneGc    material  =    
nucleocapsid  
•  virion:  complete  virus  
•  some  have  CHOs  and  lipids    
General  ProperGes  
•  genome  composiGon  
DNA  or  RNA    
(ds  or  ss)  
           
retrovirus  =  RNA  genome,    
                                             DNA  intermediate  
 
hepaGGs  B  virus  =  DNA  genome,                  
                                                                     RNA  intermediate    
General  ProperGes  

•  exist  in  2  phases  

 
   extracellular  =    can t  reproduce    
                                     (w/  few  or  w/out  enzymes)  
 

   intracellular  =    exists  as  replica3ng  NA  

                                                                                     
Host  Range  

humans other vertebrates invertebrates

plants fungi bacteria

Some  viruses  are  useful…  

Phage  typing  of  

bacteria  
Some  viruses  are  useful…  

Used  as  pesGcides    

 
   1.  myxoma  virus  for  rabbits    

 
   2.  baculovirus  for  insect  pests  
Some  viruses  are  useful…  

Sources  of  enzymes  

 
1.  Reverse  transcriptase  of    
         retroviruses    
 
2.  RNA  polymerase  of  phages  
Some  viruses  are  useful…  

Phages  as    
anGbacterial  agents  
Some  viruses  are  useful…  

AnG-­‐cancer  agents  
-­‐  modified  HSV  and    
   vaccinia  virus    
Some  viruses  are  useful…  

Gene  vectors  for  protein  produc3on  and    

treatment  of  gene3c  disease  
 History  of  Virology  

“There  can  never  be  present  without  the  past”    

 Early  records…  
•  hieroglyph  from  
Memphis  (3700  BC):  
first  wriSen  record  of  
virus  infec3on  

•  Ruma  (temple  priest)      

showing  typical  clinical  
signs  of  paraly3c  
poliomyeli3s  

http://www.microbiologybytes.comm
Early  records…  

•  Siptah   (ruled   Egypt   from  

1200-­‐1193   BC)   died   at   the   age  
of  20  
•  tomb   was   excavated   in   1905,  
mu mmi fi ed   b o d y   sh o wed  
withered  leg  and  foot  extended  
like  a  horse s  hoof  
classic  paralyGc  poliomyeliGs  
Early  records…  

Pharaoh  Ramses  V  died  in  1000BC,  believed  to  

have  succumbed  to  smallpox  
Early  records…  
smallpox  was  endemic  in  China  in  1000BC  
Edward  Jenner  (1796)  
Adolf  Mayer  (1882)  

coined  the  term    

     tobacco  mosaic  disease  (TMD)  
Charles  Chamberland  (1884)  
developed  a  porcelain  bacterial  filter  
Louis  Pasteur  (1885)  

•  developed  rabies  vaccine  

•   originated  the  term          

"vaccinaGon"  
Dmitri  Iwanowski  (1892)  

first  descrip3on  of  a  filterable            

         infec3ous  agent    (TMV)  
 MarGnus  Beijerinck  (1898)  

•  confirmed  and  extended      

             Ivanowski s  results    
•   introduced  the  concept    
           of  the  virus  as  a  contagious      
           living  form  

•  contagium  vivum  fluidum  

(soluble  living  germ)  
The Father of Plant Virology
History of virology
Alfred  Loeffler   and  Paul  Frosch  (1898)  

•  first  descrip3on  of  an  animal  virus,  foot  and  

mouth  disease  virus  (FMDV)  
•  first  to  prove  that  viruses  could  infect  
animals  as  well  as  plants    
 Walter  Reed  (1900)  
•  demonstrated  that  yellow    
   fever  is  spread  by  mosquitoes    
 

•  first  to  show  that  viruses    

       could  be  spread  by  insect    
   vectors    
 

•  first  descrip3on  of  a    

   human  virus,  yellow  fever  virus    
Remlinger  and  Riffat-­‐Bay  (1903)  
iden3fied  the  rabies  virus  
Karl  Landsteiner  and  Erwin  Popper  (1909)  
•   showed  that  
poliomyeliGs  was  
caused  by  a   filterable  
agent  
 
 

•   first  to  prove  that    

           viruses  could  infect    
           humans  
 

1st  human  disease  to  be  

recognized  as  having  
 a  viral  cause  
Francis  Peyton  Rous  (1911)  
•  demonstrated  that  a  virus  (Rous  sarcoma  virus)    
           can  cause  cancer  in  chickens    
•   isolated  the  1st  tumor-­‐causing  animal  virus  
Frederick  Twort  (1915)  &  Felix  d Herelle  (1917)  
 first  to  recognize  viruses  which  infect  bacteria,    
   bacteriophages  (eaters  of  bacteria)  

Twort

d’Herelle
 1918  flu  pandemic  
•   Spanish  flu  pandemic  
 
•   unusually  severe  and  
deadly  pandemic  that  
spread  across  the  world  
 
•   50-­‐100  M  killed  people  
from  Jun  1918-­‐Dec  
1920  
 Wendell  Stanley  (1935)  

•  crystallized  TMV  and  

showed  that  it  remained  
infec3ous    
 

•   first  step  towards  

describing  the  molecular  
structure  of  any  virus    

•  Nobel  Prize,  1946  

Max  Theiler  (1938)  

•  developed  a  live  
aSenuated  vaccine  
against  yellow  fever  (17D  
strain)  using  chick  
embryos  

•  Nobel  Prize,  1951  

 Emory  Ellis  and  Max  Delbruck  (1939)  

established  the  concept  of  the  "one  step  virus  growth  

cycle"  essen3al  to  the  understanding  of  virus  replica3on    
Helmuth  Ruska  (1940)  
used  an  electron  microscope  to  take  the  first  
pictures  of  virus  par3cles    
Andre  Lwoff  et  al.  (1950)  

•  discovered  lysogenic    
           bacteriophage  

•  coined  the  term  

prophage  
 Alfred  Hershey  &  Martha  Chase    (1952)  

•  proved  that  
bacteriophage  genome  
is  nucleic  acid  
Zinder  &  Lederberg  (1952)  
demonstrated  transducGon  of  gene3c    
informa3on  
Renato  Dulbecco  (1952)  
showed  that  animal  viruses  can  form  plaques  in  
a  way  similar  to  bacteriophages    
Jonas  Salk  and    
Albert  Sabin  (1954)  
 developed  the  polio  
vaccine  
1957  

Heinz  Fraenkel-­‐Conrat  &  RC  Williams  

•  in  vitro  assembly  of  virus  (TMV)  
 
Isaacs  &  Lindermann  
•  discovery  of  interferon  
Baruch  Blumberg  (1963)  
discovery  of  hepa33s  B  virus      
Epstein-­‐Barr  (1964)  

 discovery  of  the  1st  

human  tumor  
virus,  Epstein-­‐Barr  
virus  (EBV)  
Theodor  Diener  (1967)  
first  to  describe  viroids  
 
Howard  Temin  and  David  BalGmore  (1970)  

•  discovery  of  
retroviral  reverse  
transcriptase  
 
•   established  that  
gene3c  informa3on  
can  flow  from  RNA  
to  DNA    
Frederick  Sanger  (1978)  

•  1st  viral  genome  

sequenced  (ΦX174)  
 

•  first  complete  genome  

sequence  of  any  
organism  to  be  
determined    
1979  
WHO  declared  smallpox  eradicated  
Yorio  Hinuma  et  al.  (1981)  
•  isolated  human  T-­‐cell  leukaemia  virus  (HTLV)  from  
the  pa3ents  with  adult  T-­‐cell  leukaemia  
 
•  HTLV  was  the  first  unequivocal  human  cancer  virus  
to  be  iden3fied    
Stanley  Prusiner  (1982)  
showed  that  prions  are  the  cause  of  scrapie        
 (fatal,  degenera3ve  disease  that  affects  
the  nervous  systems  of  sheep  and  goats)    
 
Luc  Montagnier  and  Robert  Gallo  (1983)  
 descrip3on  of  human  immunodeficiency  virus  
(HIV)  as  the  causa3ve  agent  of  AIDS  
1990  
•  1st  human  gene  therapy  procedure  with  a  
retrovirus  vector  
•  first  aSempt  to  correct  human  gene3c  disease  
(SCID  –  severe  combined  immunodeficiency)  
Chang  and  Moore  (1994)  
discovered  Kaposi's  sarcoma              
   herpesvirus  (HHV-­‐8)  
1997  

1st  outbreak  of  avian  influenza  A  H5N1  virus  in  

humans    occurred  Hongkong  
1997  
HAART  treatment  for  AIDS  
(Highly  Ac3ve  An3-­‐retroviral  Therapy)    
1999  
•  #  of  confirmed  HIV/AIDS  
cases  reaches  33  million  
 
•  nucleo3de  sequence  of  
largest  known  virus  
genome  completed  
P.  bursaria  Chlorella  virus  1  
2002  
Poliovirus  synthe3cally  assembled  in  the  
laboratory    
 (1st  synthe3c   organism )  

Jeronimo  Cello,  Aniko  V.  Paul  and  Eckard  Wimmer  -­‐  Science  9  August  2002:  Vol.  297  no.  5583  pp.  1016-­‐1018  
2003  

severe  acute  respiratory  syndrome  (SARS)  

outbreak  &  containment;    
rapid  iden3fica3on  of  novel  human  coronavirus  
m
2003  
 giant  Mimivirus    was  described;    
   sequenced  in  2004  
Chisari,  Rice  &  Wakita  (2005)  
propagated  hepa33s  C  virus  in  3ssue  culture  
  
Palese,  Tumpey,  Taubenberger    (2005)  
“Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus",

Science, 7 October 2005: Vol. 10 no.5745. pp. 77-80. DOI: 10.1126/science.1119392

2006  

•  Vaccine  against  human  

papillomavirus  (Merck),  
the  second  an3cancer  
vaccine  aoer  hepa33s  
vaccine  
  
2006:  Andrew  Z.  Fire  &  Craig  C.  Mello  
 

•  Gene  silencing  by  

dsRNA,  an  an3viral  
response      
 
 2008  
•  first  known  virophage  was  described:  Sputnik  
 

•   uses  helper  virus  machinery  to  reproduce  and  inhibits  

reproduc3on  of  helper  virus  
 

•   Sputnik  reproduces  in  amoeba  infected  by  mamavirus  

2009  flu  pandemic  
emergence  of  influenza  A  (H1N1)  virus  which  
spread  worldwide  
 2011  
•   Megavirus  chilensis  
discovered  
 
•   Largest  virus  (440  nm),  
with  most  complex  
genome  1.2  Mb  
 2011  

•  Rinderpest  virus  
eradicated:  first  animal  
disease  to  be  eradicated  
by  mankind  
       (second  aoer  smallpox)  
 2012  
•  Middle  east  respiratory    
syndrome  coronavirus  
•  called  nCoV  -­‐  novel  
coronavirus)  
•  first  characterized  in  2012  by  
Prof  Ali  Mohamed  Zaki  
•   1st  case  was  a  60-­‐year  old  
male  with  suspected  viral  
pneumoniaviral  pneumonia.

http://www.uq.edu.au/vdu/VDUMERSCoronavirus.htm
 2013  
Newly Discovered Giant Viruses could
be the ‘Fourth Domain’ of Life?
Posted on July 22, 2013

Pandoraviruses
infect amoebae
and are larger than
some bacteria.

http://www.technology.org/2013/07/22/newly-discovered-giant-viruses-could-be-the-fourth-domain-of-life/
Journal Reference:
N. Philippe, M. Legendre, G. Doutre, Y. Coute, O. Poirot, M. Lescot, D. Arslan, V. Seltzer, L.
Bertaux, C. Bruley, J. Garin, J.-M. Claverie, C. Abergel. Pandoraviruses: Amoeba Viruses with
Genomes Up to 2.5 Mb Reaching That of Parasitic Eukaryotes. Science, 2013; 341 (6143): 281
DOI:10.1126/science.1239181

Pandoravirus  

Size:  1.0um  
 
Genome:  2.8Mb  
Pithovirus sibericum

Size: 1.5um
Genome:0.6Mb
2014  
“The  return  of  the  Ebola    
virus  disease”  
 
1st  outbreak:  1976  
(Sudan,  Congo-­‐  Ebola  
River)  
 
Fatality  rate  up  to  90%  
 
(previously  known  Ebola  
hemorrhagic  fever)  
2016  

HIV  in  the  

Philippines  
2015-­‐2016:  Zika  virus  epidemic