Identifying the weak spots in both your defenses and your adversary’s is a standard military strategy that has been employed for several millennia. Yet, for infectious disease researchers, locating the molecular entry points for various viral and microbial diseases can be akin to finding a needle in a haystack. However, scientists at Northwestern University have now been able to visualize where HIV enters the female reproductive tract by creating a glowing map of the very first cells to be infected with an HIV-like virus.
Using rhesus macaques and a simian immunodeficiency virus (SIV), which is generally considered to be analogous to HIV, the researchers have shown 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,” explained senior study author Thomas Hope, Ph.D., professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. “Now we know which areas are vulnerable to HIV and can investigate why does the virus get in here and not everywhere else?”
The findings from this study were published recently in Cell Host & Microbe in an article entitled “Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.”
“If we are going to stop women from getting infected, we have to stop the very first cells from getting infected,” noted Dr. Hope. “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.”
The Northwestern researchers stripped away much of the genetic material from the HIV-like virus and inserted a luciferase gene from fireflies, as well as another gene from a fluorescent protein, to generate a reporter virus. The scientists then subsequently mixed the reporter virus with live SIV. The glowing cells infected by the reporter revealed the site of infection with the live virus.
Surprisingly the investigators found that after being transmitted to the host, the nonengineered virus appeared in clusters of about 20–30 infected cells within 48 hours. Without the new technology, “scientists would have to take a million little sections to see if they found evidence of the virus,” Dr. Hope remarked.
Dr. Hope and his colleagues are optimistic that their discovery will help scientists 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,” Dr. Hope stated. “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.”
The Northwestern team was able to identify that the primary target of viral transmission is the Th17 cell, a minority but significant population of T cells in the first line of immune defense. It was previously known that these cells are depleted early in HIV and SIV infections—within 48 hours of infection, scientists have seen evidence of viral depletion of Th17 cells.
“We can see infected dead cells, infected cells being eaten by other cells to control them, and cells that kill themselves (apoptosis),” Dr. Hope stated. “The virus is causing all those things, and it shows the battle between the virus and infected host begins immediately upon infection.”