Download Part human, Part hIV

HIV
Part human, part HIV
Lucy reading-Ikkanda for The Scientist, June 2011
Like other enveloped viruses, HIV exits its host cell enshrouded
in the cell’s membrane, which contains membrane molecules
such as the human leukocyte antigens (HLA). The HLA proteins
act as a set of cell identification marks: every person expresses
a slightly different HLA set. These molecules differentiate one
person from another and allow the immune system to detect foreign invaders, and to reject tissue from other people or animals.
Interestingly, each HIV particle has many more human HLA on
its envelope surface than it has its own gp120 viral coat proteins,
which the virus needs to bind to CD4 and CCR5 or CXCR4 on the
lymphocyte surface in order to enter cells.
Infected human
CD4 T cell
HIV particle
HLA on surface
of HIV particle
HLA on surface
of human cell
Alloantigen based AIDS vaccine (ABAV)
An HLA vaccine could consist of both inactivated HIV grown from
lymphocytes expressing an array of HLA molecules 
1 . The vaccine
would be taken up by dendritic and other antigen-presenting cells 
2, ,
which would trigger both an innate response, and adaptive responses
such as the production of antibodies specific for the foreign HLA 
3.
During an infection, the antibodies would bind to the HIV particles’ HLA,
marking it for elimination 
4 . Antibodies to CCR5 would also be made,
which help block viral entry 
5 . If the virus bypassed these extracellular
barriers, the innate response would create additional barriers and
defenses: The b-chemokines MIP-1a, MIP-1b, and RANTES would block
the HIV coreceptors CCR5 and CXCR4. Once inside the cell, intracellular
factors EDN and APOBEC3G would damage the viral RNA, preventing it
from properly replicating 
6 . This one-two punch would, in theory, be
enough to stop a viral infection.
Diverse
HLA
Inactivated
HIV particle

1
Dendritic
cell

2
T cell
Cytokines
Plasma
cells
b chemokines
(MIP-1a, MIP-1b
and RANTES)
Diverse
HLA
antibodies
produced

3
CCR5
antibodies
produced
Viral RNA is
damaged and HIV
is neutralized

6
CCR5 receptor
HIV is
neutralized by
antibodies

4
HIV cannot
enter cell
Human CD4 T cell
is protected from
HIV infection

5
CXCR4
receptor
EDN and
APOBEC3
are activated
Self-HLA
06.2011 | The Scientist