2000 ASCB Annual Meeting Press Book - page 7

Breaking and Entering:
How HIV Makes First
Contact
Most therapeutic strategies against the AIDS virus aim to
stop the deadly game of viral hide and seek that occurs
after cells are already infected by HIV. Additional strategies
would result from a better understanding of how HIV first
enters the body. HIV is usually first transmitted through
either sexual contact or breast-feeding to epithelial cells that
line body openings such as the gastrointestinal, ano-rectal,
and genitourinary tracts. Two French researchers, Annette
Alfsen and Morgane Bomsel, have taken a closer look at the
first steps of infection using a tight epithelial monolayer that
mimics a simple epithelium.
The first aim of the HIV virus is to get past the layers of
epithelial cells and reach target cells buried deep in the
‘submucosa’ region of the skin. HIV can pass straight
through the epithelial cells, without actually infecting them,
to attack the cells beneath. To do this, HIV takes advantage
of a natural pathway called transcytosis. During transcytosis,
proteins or particles on the outside of a cell are taken into
membrane-bound vesicles, ferried through the cell, and
released at the other side of the cell. HIV-infected cells pres-
ent in seminal fluid, vaginal secretions or milk are ‘sticky’,
and can bind directly to the outer layer of epithelial cells.
This contact induces the production and release of infec-
tious virus particles, which are taken up and transcytosed
through the epithelial cells to emerge on the other (‘serosal’
or ‘blood’) side of the epithelium. In less than an hour, tran-
scytosed viruses can reach the host’s submucosal mononu-
cleated target cells, where they can establish the infection.
Alfsen and Bomsel believe they have found a way to
possibly block this invasion route for HIV. To enter epithe-
lial cells, HIV uses the two subunits of its envelope glyco-
protein in a cooperative manner to bind a specific receptor
at the epithelial cell surface. This receptor is a complex mol-
ecule that is half-lipid, half-sugar: a glycosphingolipid
named galactosyl ceramide. Transcytosis of HIV was
blocked by treatments that disrupted the assembly of sur-
face microdomains that contained galactosyl ceramide.
Importantly, the French scientists have found an antibody
that is secreted in mucous, that binds specifically to a region
in one of the HIV envelope glycoprotein subunits that is
conserved among the many subtypes of HIV. This antibody
can block HIV binding to the receptor and also blocks HIV
transcytosis, thus offering a way to slam the door shut on
HIV. Immunization against this region of HIV may provide
an important future means of controlling the spread of this
virus.
2
40th Annual Meeting
December 9-13, 2000
Moscone Convention Center, San Francisco
Contact:
Morgane Bomsel
Telephone: (33) 1-40-51-64-97
HIV Transcytosis across epithelial cell
depends on galactosyl ceramide and lipid
dynamics of the apical membrane
Authors:
Annette Alfsen and Morgane Bomsel
U332 Institut Cochin de Genetique
Moleculaire
22 rue Mechain
75014 Paris, FRANCE
target of
infection-preventing
mucosal antibody
viral
membrane
hydrophobic
region
gp41
subunit
gp 120-epithelial cell
binding site
gp 120
subunit
gp41-epithelial cell
binding site
Ca
2+
binding
site
At The ASCB Meeting
Poster Session Halls A/B/C
P137 - Exocytosis: Plasma Membrane Events
Author Presents
Wednesday, December 13, 12:00 PM-1:30 PM
Program # 2576
Board # B109
Oligomeric organization of the HIV envelope glycoproteins.
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