SEATTLE, Feb. 15 /PRNewswire/ -- The primary targets of HIV-1 infection
in the human vagina have been definitively identified in a new study
published in the February 2007 issue of the journal Immunity, published by
Cell Press. The findings are likely to guide development of new strategies
that will prevent HIV-1 transmission.
"The majority of HIV-1 infected individuals worldwide are women who
acquire HIV infection following sexual contact," said study authors Florian
Hladik, M.D., Ph.D.; and M. Juliana McElrath, M.D., Ph. D, both of Fred
Hutchinson Cancer Research Center. "Blocking HIV transmission and local
spread in the female lower genital tract is key to prevent infection and
ultimately to ease the pandemic."
Hladik and colleagues in the McElrath laboratory developed a unique
model system to study the precise mechanisms by which HIV-1 enters the
lower reproductive tract of human females. The researchers separated and
removed the outer lining of vaginal cells, which serves as the first
barrier to the virus. The isolated preparation of intact, viable, vaginal
epithelium permitted examination of immune cells that normally migrate out
of the vaginal epithelium into deeper tissues shortly after exposure to
HIV-1.
The researchers found that HIV-1 simultaneously enters two different
types of intraepithelial cells associated with the immune system,
Langerhans cells (LC) and CD4+ T cells. However, the path of entry and rate
of infection was different for the two cell types. Infection of CD4+ T
cells appears to rely at least in part on expression of major HIV-1
coreceptors such as CCR5, whereas pathways for infection of vaginal LC
appear to be more diverse and complex. In contrast to previous studies,
infection of CD4+ T cells does not appear to require passage of the virus
from LC.
Both LC and CD4+ T cells can migrate out of the vaginal epithelium.
Study findings suggest that CD4+ T cells may be principally responsible for
local shedding of the virus in the vagina of women infected with HIV-1
while LC may harbor viable virus for some time before spreading it to other
cells.
These results reveal that it is necessary to consider mechanisms of
viral entry into both CD4+ T and LC when searching for an effective way to
interfere with infection through the vaginal epithelium.
"Our findings provide exciting definitive insights into the initial
events of HIV-1 infection in the human vagina, which can guide the design
of effective strategies to block local transmission and prevent HIV-1
spread," McElrath said.
The study was supported by NIH grants AI51980, HD51455 (F.H.), AI35605
(M.J.M.), and AI27757 (University of Washington CFAR); a Burroughs Wellcome
Translational Research Award (M.J.M.); and the James B. Pendleton Trust
(F.H. and M.J.M.). Publishing in Immunity, Vol. 26, Issue 2 February, 2007.
http://www.immunity.com
McElrath is a member of the Clinical Research Division and the program
in infectious diseases at the Hutchinson Center, as well as a professor of
allergy and infectious diseases at the University of Washington School of
Medicine. Hladik is an associate in clinical research at the Center and a
research assistant professor of medicine and allergy and infectious
diseases at the University of Washington School of Medicine.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit fhcrc.org.
CONTACT
Dean Forbes
(206) 667-2896
dforbes@fhcrc.org
SOURCE Fred Hutchinson Cancer Research Center
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CONTACT:
Dean Forbes of Fred Hutchinson Cancer
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