Videos reveal how HIV spreads in real time

How retroviruses like HIV spread in their hosts had been unknown — until a Yale team devised a way to watch it actually happen in a living organism. The elaborate and sometimes surprising steps the virus takes to reach and spread in the lymph nodes of a mouse have been captured on videos and described in the Oct. 2 issue of the journal Science.

“It’s all very different than what people thought,” said Walther Mothes, associate professor of microbial pathogenesis and co-senior author the paper.

Tracking fluorescently stained viruses in mice, the Yale team led by Mothes and co-senior author Priti Kumar, assistant professor of medicine and microbial pathogenesis, used sophisticated imaging technology to capture the action as the viral particles bind to macrophages via a sticky protein that is located at the capsule of the lymph node (in blue).

To directly visualize the fate of HIV and related retroviruses at lymphoid tissues, Xaver Sewald, Walther Mothes and collaborators directly visualized fluorescently labeled viruses at the lymph node of an anesthetized mouse. They find that a specific macrophage type captures virus particles through a sticky surface protein CD169/Siglec-1 that binds the glycolipids in the virus shell. These macrophages then pass on the virus to infect permissive lymphocytes. This process, also called trans-infection, is needed for the virus to efficiently infect a mouse. Taking videos of this process in a living mouse, the team can visualize single steps of how this occurs for a mouse retrovirus MLV. In Movie 2, virus (in Green) is seen as it arrives at the lymph node and is captured by a layer of macrophages. The lymph node capsule is in blue.

But that is only the first step of the journey. The captured viral particles open to a rare type of B-cell, seen in red in the accompanying movie. The virus particles then attach themselves to the tail of these B-cells and are dragged into the interior of the lymph node. In one to two days, these B-cells establish stable connections with tissue, enabling full transmission of the virus.

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The insights provided by the videos identify a potential way to prevent HIV from infecting surrounding tissue. If researchers could develop a way to block the action of the sticky protein the virus uses to bind to macrophages, then the virus’ transmission could be halted, Mothes suggested.

“The direct study of viral pathogenesis within living animals should reveal more surprises in the future,” Mothes said.

Postdoctoral researcher Xaver Sewald is lead author of the paper. Pamela Bjorkman of Cal Tech also contributed to the research, which was funded by the National Institutes of Health, The Leopoldina German National Academy of Sciences, and the China Scholarships Council.