sexta-feira, 4 de fevereiro de 2011

HIV-like infection banished from mice

For the first time, an HIV-like infection has been cleared from an animal without the use of antiviral drugs. The infection was eliminated from mice using a human protein that peps up immune cells.
Marc Pellegrini from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and colleagues infected mice with lymphocytic choriomeningitis virus (LCMV), which causes a chronic infection that spreads throughout the body. "The virus overwhelms mice, mimicking the massive viral loads associated with HIV infection in humans," says Pellegrini.
Eight days after infection, some of the mice were injected with human interleukin-7 (IL-7) – a chemical messenger that plays a role in the development of immune cells – once a day for three weeks. The others received a placebo instead.
"Usually mice never clear this virus," says Pellegrini. But 30 days later, those given treatment had cleared most of the infection and removed all of it by 60 days.

Overactive response

The explanation seems to lie in a protein called SOCS3, which blocks the function of T-cells – a type of immune cell and therefore part of the body's system for fighting infection. At the beginning of an acute infection, SOCS3 becomes highly activated, suppressing the body's immune response. That sounds just the opposite of what you'd want. But it's a good thing because it stops T-cells being overzealous, which can cause damage to body tissue, says Pellegrini.
It becomes a problem when the body is trying to fight an overwhelming infection like HIV, he says: then the immune system puts on the brakes too early and the infection persists.
Blood tests taken throughout the experiment showed that IL-7 seemed to switch off the production of SOCS3, thereby ramping up the T-cell response.

Start and stop

This explanation was confirmed when the team knocked out the SOCS3 gene in a separate group of mice and infected them with LCMV. Immune cell numbers in these mice skyrocketed – T-cells increased sixfold compared with normal mice.
But knocking out SOCS3 showed the dangers of taking the immune brakes off. "Initially the mice mounted a robust immune response, but then it got out of hand," says Pellegrini. The mice developed mass inflammation and increased incidences of autoimmune diseases.
However, because IL-7 only affects T-cells, and not other types of immune cell, the researchers suggest that drugs could be developed that turn offSOCS3 for very short periods to reinvigorate T-cells without causing damage to the body.
Sharon Lewin at the Burnet Institute in Melbourne says the finding that IL-7 can clear the virus without the help of antiviral drugs is very interesting. Viruses like HIV use the host's cells to replicate, which makes it difficult to design antivirals that stop the virus without harming healthy cells.
"[Stopping a virus] without antivirals is something we haven't seen before," she says.

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