One of the first things HIV does when it first enters the body is mess up the gut. Now, the open access journal PLOS Pathogens reports the first 3D ultra-structural study of the human immunodeficiency virus in a live host.
The human gut has the highest concentration of HIV target immune cells, most of which the virus destroys within days of infection. This happens even before a measurable drop of immune CD4 T cells occurs in the bloodstream.
Studies using high-resolution imaging of HIV-infected tissue have revealed details of the structure of HIV-1, the virus that causes AIDS, and have demonstrated how it infects cells and accumulates in different tissue sub-structures.
But until now, these have been confined to infected cultured cells or purified virus.
In this new study, a team led by Pamela Bjorkman, a professor of biology at the California Institute of Technology, has - for the first time - used 3D electron microscopes to show active HIV infection in the gut of mice with humanized immune systems infected with HIV-1.
HIV particles bud from host cells and gather in pools
The study is important because it shows how HIV behaves in infected tissue that closely resembles the gut of human patients.
Pools of mature HIV-1 virions populate intercellular spaces highlighted by segmentation (blue: viral envelope, magenta: conical cores).
Image credit: Ladinsky et al.
While some of the findings confirm earlier ones from cultured cell studies, there are also some results that have not been seen before, revealing new insights about how HIV spreads in real life.
For example, the researchers caught virus particles in the act of budding from their host "virus-factory" cells and gathering in pools between cells.
From one such cell, they counted 63 virus particles that it had most likely released.
The team suggests the host cells probably produce more than this, but because their method cannot show particles further away from the cell, they could not prove it.
But they were able to deduce that virus particles they could see furthest from the host cell were more mature than those closest to it, which made them think the cell releases them in waves.
'Synapses' may not be the major route of HIV transmission
Additionally, the team found that not only do some released virus particles attach directly to neighboring host cells - in what are termed "virological synapses" - but also others appear to travel quite far from their "mother" cell to the target cell.
Prof. Bjorkman, who is also a Howard Hughes Medical Institute investigator, says for her, this was an important finding:
"The spread of viruses through synapses had been speculated to be a major route of transmission in tissue, but our results reveal large pools of free virions. This discovery provides hope that possible therapeutics, such as antibodies, would be able to access infecting viruses that are not hidden within a virological synapse."
In 2012, Medical News Today reported on a study that also revealed how immune cells in the gut help control HIV growth.
Written by Catharine Paddock PhD