Infec&on

 basics
Week  1,  Session  1  
How  viruses  cause  disease  
Prof.  V.  Racaniello
The  nature  of  host/parasite  interac1ons

The  viral  genome  must  establish  itself    

in  a  host  popula4on  to  endure
©2009  ASM  Press
 Basic  facts

• Every  host  alive  today  has  intrinsic  defenses  coupled  

with  immune  defenses  that  evolved  to  deal  with  
infecGons  and  tumors  
• Every  successful  virus  today  must  modulate  host  
defenses  to  replicate  and  disseminate  
• These  host-­‐virus  interfaces  define  the  front  line  of  
survival  for  both  host  and  virus
We  live  and  prosper  in  a  literal  cloud  of  viruses

• Most  infecGons  have  no  consequence  

-­‐ Many  parGcles  never  find  a  living  cell  to  infect  (land  on  your  skin)  

-­‐ Many  are  destroyed  or  inacGvated  as  they  enter  the  host  

-­‐ Many  infecGons  never  go  further  than  one  or  two  cells  at  the  site  of  infecGon  

• If  we  do  get  infected,  many  infecGons  are  inapparent  

-­‐ No  symptoms,  but  immune  defenses  are  acGvated  (e.g.  anGbodies  made  -­‐  this  is  how  we  
know  there  are  inapparent  infecGons)  

-­‐ Virus  may  be  replicaGng  and  transmiRed  during  these  inapparent  acute  infecGons
 Example:  West  Nile  virus  infec1on

• WNV  spread  across  the  US  in  less  than  4  years  (’99)  
-­‐ By  October  2004  about  1  million  people  were  infected  (anGbody  posiGve)  
-­‐ Febrile  illness  developed  in  about  20%  of  infected  people  
-­‐ Neuroinvasive  illness  developed  in  about  1%  of  infected  people  

• Many  people  were  infected  with  no  obvious  disease  

-­‐ Transmission  of  disease  via  blood  transfusion  or  organ  transplants  
-­‐ Inability  to  stop  an  epidemic  because  it  can’t  be  recognized  early
 Microbes  as  infec1ous  agents

• Poisonous  air  (miasma)  was  believed  to  account  for  

epidemics  of  contagious  disease  
• AssociaGon  of  microorganisms  with  disease  arose  
from  work  of  German  physician  Robert  Koch  
(1843-­‐1910)  
• Koch  developed  and  applied  a  set  of  criteria  for  
idenGfying  the  agent  responsible  for  a  specific  disease  
-­‐  a  pathogen
 Yellow  fever  virus  -­‐  first  human  virus,  1901

Carlos  Finlay

Jesse  Lazear

Walter  Reed

©2009  ASM  Press

 Fundamental  ques1ons  of  viral  pathogenesis

• How  does  a  virion  enter  the  host?  

• What  is  the  iniGal  host  response?  
• Where  does  primary  replicaGon  occur?  
• How  does  the  infecGon  spread  in  the  host?  
• What  organs  and  Gssues  are  infected?  
• Is  the  infecGon  cleared  from  the  host  or  is  a  persistent  
infecGon  established?  
• How  is  the  virus  transmiRed  to  other  hosts?
 Three  requirements  for  ensuring  a  successful  
infec1on

• Sufficient  virus  parGcles  must  be  available  

• The  cells  at  the  primary  site  of  infecGon  must  be  
accessible,  suscepGble,  and  permissive  
• Local  host  anGviral  defense  systems  must  be  absent  or  
overcome
 Sufficient  virions  at  the  site  of  infec1on

• How  many  virions  does  it  take  to  infect  a  host?  

-­‐ Varies  for  every  virus/host  interacGon  
• Many  variables  conspire  to  complicate  the  issue  
-­‐ Host  geneGcs  (outbred  populaGons)  

-­‐ Host  anGviral  defenses  

-­‐ Viral  virulence  

-­‐ Host  social  behavior  

-­‐ Age  of  host  

-­‐ Weather/environment
 Virion  defenses  to  hos1le  environment

• Many  virus  parGcles  are  sensiGve  to  heat,  drying,  

sunlight  (UV)  
-­‐ Overcome  by  producing  huge  numbers  of  virions  

• Many  virions  are  stable  to  low  pH  or  proteases  

-­‐ Survive  in  gut;  fecal-­‐oral  transmission  (water  borne)  

• Many  virions  never  experience  the  environment  

-­‐ Life  cycles  involve  insect  vectors  

• Many  infecGons  spread  by  physical  contact  

-­‐ Transfer  by  body  fluids;  virions  not  outside  for  long
 Viral  pathogenesis

• Pathogenesis:  the  process  of  producing  a  disease  

• Two  components  of  viral  disease:  
-­‐ Effects  of  viral  replicaGon  on  the  host  
-­‐ Effects  of  host  response  on  virus  and  host  
• Virus  infecGons  span  the  range  from  benign  to  lethal  
-­‐ Acute  and  persistent  infecGons  can  be  quick  or  
amazingly  slow  -­‐  days  to  years  of  infecGon
 Images  from  Principles  of  Virology  
©2009  American  Society  for  Microbiology  
Are  used  with  permission  
No  further  reproducGon  or  distribuGon  is  permiRed  
without  the  prior  wriRen  permission  of  the    
American  Society  for  Microbiology