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An immune system protein normally found in semen
appears to enhance the spread of HIV to tissue from
the uterine cervix, according to researchers at the
National Institutes of Health.
The protein interleukin 7 (IL-7) belongs to a family
of proteins that regulate the immune response. IL-7
is present in normal semen, and occurs at especially
high levels in the semen of men with HIV.
The researchers developed a culture system of small
pieces of tissue from the cervix and used this
system to simulate male-to-female transmission of
HIV, which causes AIDS. They observed the spread of
the virus in cervical tissue under controlled
laboratory conditions.
In the presence of IL-7 at levels typically found in
semen of men with HIV, the virus spreads to the
tissue more readily than it spreads to tissue not
treated with IL-7.
According to the study authors, the finding raises
the possibility that IL-7, alone or in combination
with other molecules, can foster male-to-female
transmission of HIV. Similarly, they note, it’s
possible that the level of IL-7 in semen may
determine how infectious a particular HIV-positive
male is for a female sexual partner. Also,
researchers may one day be able to prevent or delay
the spread of HIV by blocking seminal IL-7.
The major targets for HIV infection are T cells, a
type of immune cell that normally marshal the body’s
defenses against disease-causing organisms.
Generally, when these cells become infected with
HIV, they quickly die before the virus can produce a
large number of copies of itself. However, the
researchers found that in isolated pieces of
cervical tissue, HIV-infected T cells in the
presence of IL-7 live longer and so continued to
produce the virus. IL-7 also stimulated uninfected T
cells to divide thus increasing their number. These
new T-cells would provide additional targets for the
virus, potentially increasing its spread.
Researchers have long known that biological
interactions that take place in the laboratory may
not always occur in the more complex environment of
a living organism. For this reason, Dr. Margolis
noted that additional studies would be needed to
confirm what he and his coworkers observed in the
laboratory.
“These experiments show us again how vicious HIV
is,” said senior author Leonid Margolis, Ph.D., head
of the Section on Intercellular Interactions at the
Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), where the
research was conducted. “The virus is able to
commandeer an immune protein for its own benefit.”
Based on their results with IL-7, Dr. Margolis said,
his team plans to investigate whether other immune
system proteins present in semen are involved in HIV
transmission.
Their findings appear in PLOS Pathogens.
The paper was co-authored by Andrea Introini,
Christophe Vanpouille, Ph.D., Andrea Lisco, M.D.,
Ph.D., Jean-Charles Grivel, Ph.D., and Leonid
Margolis, Ph.D., all of the NICHD. Mr. Introini also
is a Ph.D student at the University of Milan, Italy.
For more information
http://www.nichd.nih.gov/
Interleukin-7 Facilitates HIV-1 Transmission to
Cervico-Vaginal Tissue ex vivo
(MDN)
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