Finding the vulnerable points where HIV enters the female reproductive tract has been a challenge. But a glowing map of the very first cells to be infected with a HIV-like virus has helped scientists solve the mystery.
They showed for the first time that HIV enters cells throughout the entire female reproductive tract from the labia to the ovary, not just the cervix, as previously thought.
“It’s a technical achievement that provides immediate insights into the earliest transmission events. Now we know which areas are vulnerable to HIV and can investigate why does the virus get in here and not everywhere else?,"
says lead investigator Thomas Hope, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine.
“If we are going to stop women from getting infected, we have to stop the very first cells from getting infected,” Hope says. “A week after the initial infection, there are hundreds of thousands of infected cells, and it’s very difficult to stop. If you can stop it earlier, then you have a chance.”
Any strategies to efficiently prevent HIV acquisition in women likely needs to protect the entire female reproductive tract.
Glowing Cell Clusters
For the new study scientists removed the guts from the virus and inserted a gene from lightning bugs and another gene from a fluorescent protein to generate a reporter virus.
Then they mixed the reporter virus with the real HIV-like virus. The glowing cells infected by the reporter revealed the site of infection with the real virus. The result: after being transmitted to the host, the real virus appeared in clusters of about 20 to 30 infected cells within 48 hours.
[caption id=“attachment_28023” align=“aligncenter” width=“640”] The illustration shows that infection of target cells can take place throughout the female reproductive tract. And at all sites the primary target of early infection is Th17 cells. The Th17 cells are identified by the markers of CCR5 and CCR6. The infected cells are illustrated by the white burst. Courtesy of Northwestern University.[/caption]
Without the new technology, “scientists would have to take a million little sections to see if they found evidence of the virus,” Hope says.
For the study, scientists used rhesus macaques and a simian immunodeficiency virus (SIV) that is generally analogous to HIV. They say the discovery will help design a more effective vaccine to protect women from HIV.
“For a vaccine to be effective, you don’t just need your arsenal of weapons but they need to be in the right place at the right time,” Hope says. “If you show up a day late or don’t bring enough weapons, it’s too late. Now we can see the chink in the armor of the virus. If you can attack it early instead of late, you can stop it.”
Scientists discovered the primary target of transmission is the Th17 cell, a minority but important population of T cells in the first line of immune defense. It was previously known that they are depleted early in HIV and SIV infections.
Within 48 hours of infection, scientists can see evidence of the battle between the virus and the Th17 cell.
“We can see infected dead cells, infected cells being eaten by other cells to control them, and cells that kill themselves (apotosis),” Hope says. “The virus is causing all those things, and it shows the battle between the virus and infected host begins immediately upon infection.”
Daniel J. Stieh , Edgar Matias , Huanbin Xu , Angela J. Fought , James L. Blanchard , Preston A. Marx , Ronald S. Veazey , Thomas J. Hope Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques Cell Host & Microbe; DOI: http://dx.doi.org/10.1016/j.chom.2016.03.005
Image: Moyan Brenn/Flickr