HIV/AIDS Research Update

December 12, 2013

We’re  excited  to  have  one  of  our  newest  board  members  contribute  to  this  issue  of  The Update! They  have  offered  to  break  down  the  often  complex  news  that  comes  out  of  the  medical  field  into  terms we  can  all  understand.

 

Happy  fall,  fellow  PWAC  members  and  friends! With this new season comes new research  and breakthroughs  relating  to  the  control  and  treatment  of HIV/AIDS.   I have been asked  to help  break  down  the  big  stories  in  the  research  realm  and share the discoveries with you all each month.   This month,  I have selected  three separate articles  to  discuss,  each  having  made  great  strides  in  the  clearance/eradication of  the virus in the lab.  Each  group  has  a  great  deal  more  work  to  do,  but  the  news is exciting nonetheless!

 

First  up,  I  am  going  to  discuss  work  performed  at  the  Picker  Lab  at  the  Oregon  Health  and Science University, in which  they were able  to  completely  clear  SIV  (Simian  Immunodeficiency  Virus) from monkeys, the virus that causes AIDS in  this  species (Hansen et al.,  2013 . The  researchers  at the Picker Lab utilized an interesting approach to  treatment;  instead  of  using  drugs  to  prevent  viral  replication,  they  utilized  a  genetically  engineered  version of a common virus, cytomegalovirus (CMV),  to  trigger  a  stronger  and  maintained  immune  response from effector memory T cells. These cells have  the ability  to  “remember”  harmful  pathogens  indefinitely  This  is  the  technique  employed  by  many  vaccines  to  provide  long-term  protection.  Unfortunately,  the  typical immune  response  to  the  wild-strain SIV/HIV is  not effective at  clearance  of  the  virus.  The  altered  CMV  used in  the  Picker  Lab  expressed  specific  SIV  proteins,  and  the  body  responded by introducing new T -cells that have the  ability  to  successfully  identify  and  destroy  SIV- infected  cells.  These  new  T-cells  then  act  as  “security  guards”  and  work  to  clear  the  threat,  in  time eliminating the virus from the body.  Although  only  50   of  the  animals  in  the  study  had  full  clearance,  the  group  hopes  to  learn  why  this  was  and  ultimately  to  develop  an  effective  vaccine  strategy  in  the  future  using  this  newly  discovered  data.

 

The  next  article  to  discuss  comes  from  Rutgers New Jersey Medical School, lead by Michael  Matthews and Hartmut Hanauske-Abel (Hanauske- Abel  et  al.,  2013).    Using  in vitro   (meaning  “in  glass”)  cell  cultures,  they  were  able  to  determine  the efficacy  of  using a  common  topical anti-fungal,  Ciclopirox,  as  a  means  to  eradicate  HIV  infected  cells.  Interestingly,  the  anti-fungal  drug  causes  the  HIV-infected  cells  to  spontaneously  commit  “suicide”  by  blocking  the  critical  functions  of  the  mitochondria,  the  powerhouse  of  the  cell.  HIV-1  typically  blocks  this  “suicide-pathway”  (known  as  apoptosis)  in  infected  CD4  cells,  preventing  the  body from protecting itself. The introduction of this  drug  reactivates  this  natural  cell  behavior  while  leaving  healthy,  uninfected  cells  unaffected.  Although  Ciclopirox  is  already  FDA  approved,  it’s  for  topical  use  only;  so  the  researchers  at  Rutgers  are  eager  to  investigate  a  similar  new  drug,  Deferiprone, which is  aimed  towards  systemic  use  and is currently in human trials in Africa. This new  drug  has  also  shown  efficacy  in  HIV  clearance  in vitro.  Stay tuned to these folks; they are headed in  the right direction!

 

The final article I have selected to discuss is  one  recently  published  by  a  team  led  by  Cameron  Abrams  and  Irwin  Chaiken  at  Drexel’s  College  of  Medicine (Contarino et al., 2013).  Using a chimeric  recombinantly  engineered  protein  (a  fancy  way  of  saying  a  molecule  or  protein  built  from  smaller  pieces  of  molecules/proteins  for  a  specific  application),  the  group  was  able  to  activate  HIV’s  fusion  trigger,  providing  the illusion  that  the  virus  is affixed  to a healthy cell. This  trigger  then causes  the virus to “pop,” or eject, its viral genetic material  into the abyss of the human body, rather than into a  healthy  CD4  cell, essentially  tricking  the  virus into  “spilling its guts” harmlessly and dying. Unless  the  viral  genetic  material  is  delivered  directly  into  a  healthy  CD4  cell,  replication  is  not  possible;  thus  viral  load  is  ultimately  suppressed.    Very  cool  indeed!

 

Contarino, M., Bastian, A. R., Sundaram, R. V. K., McFadden, K., Duffy, C.,  Gangupomu, V., et al. (2013). Chimeric Cyanovirin-MPER  Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1.  Antimicrobial Agents and Chemotherapy, 57(10), 4743–4750.  doi:10.1128/AAC.00309-13

Hanauske-Abel, H. M., Saxena, D., Palumbo, P. E., Hanauske, A.-R., Luchessi, A.  D., Cambiaghi, T. D., et al. (2013). Drug-Induced Reactivation of  Apoptosis Abrogates HIV-1 Infection. PloSone, 8(9), e74414.  doi:10.1371/journal.pone.0074414

Hansen, S. G., Jr, M. P., Ventura, A. B., Hughes, C. M., Gilbride, R. M., Ford, J. C., et  al. (2013). Immune clearance of highly pathogenic SIV infection. Nature.  doi:10.1038/nature12519

 

 

 

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