We've been given the first glimpse of HIV in attack mode in the gut, shedding light on how the virus hijacks immune cells, multiplies and spreads throughout the body.
A team of biochemists have used electron tomography microscopes to capture the first high-resolution, 3D images of the HIV virus lurking in the intestines of "humanised" mice, whose immune systems are made up largely of human cells.
"This is the next step in studying how the virus interacts with immune cells in its natural environment, not in a Petri dish" says Mark Ladinsky, part of the team at the California Institute of Technology that carried out the work.
Although it was known that HIV hides out in the gut, Ladinsky says no one had expected to find such large pools of circulating virus.
In this video reconstruction, the team presents a sequence of intestinal cross-sections just 0.9 nanometres thick taken from a deep region of intestinal tissue that houses immune cells. These are called intestinal crypts, after their pocket-like shape.
The microscopic images are laid on top of one another to give the viewer a "zoom through" look at spherical particles of HIV virus (labelled in blue) within a small tissue volume.
Two immune cells called CD4 T-cells that have been infected with HIV lie side by side, taking up most of the frame. The HIV has commandeered the immune cells and new viruses bud from the cell surfaces to join a pool of more than 300 free, mature HIV particles circulating in the space between the cells.
In the second part of the clip, the gut tissue disappears to show only the pool of virus, which is rotated in 3D to demonstrate the spread of HIV within the intestinal crypt.
HIV house
Studying the large pools of virus in these crypts is crucial to understanding HIV's rapid spread, Ladinsky says. The intestinal tissue, which houses 70 per cent of the body's immune cells, is one of the first regions that HIV attacks. Within the first month of infection, the virus can ravage more than 50 per cent of the intestinal tissue's CD4 T-cells.
The high concentration of virus in the crypts, Ladinsky says, may help to explain the rapid immune cell destruction they cause. The crypts are a reservoir for HIV in people with the virus, he says, allowing the virus to avoid any antiretroviral drugs circulating in the blood. This makes the tissue an important focus for researchers developing therapies to flush out the virus.
Wes Sundquist, a biochemist at the University of Utah in Salt Lake City, says the study is a technical feat. Producing an image with a fine-enough resolution to see an object as small as an HIV virus is notoriously difficult to achieve for delicate tissue samples, he says.
"The next step is to try and image what HIV virus looks like in the intestines of human patients, especially in those who are taking antiretroviral drugs and those who can control it on their own," he says.
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