A gene from fireflies has been used to challenge conventional wisdom on how HIV is sexually transmitted to women. The information is necessary to design better methods of protection, and the technique could be applied to other infectious diseases.
In the constantly evolving arms race between pathogens and our immune system, skin, generally speaking, is an excellent defense against invaders. Even the more vulnerable parts of our body have developed plenty of tricks to keep threats out. Consequently, it is often difficult to work out how viruses find their way to places they can multiply.
In the case of HIV virologists believed that, during heterosexual sex, it is passed from men to women through the cervix. However, when Professor Thomas Hope of Northwestern University tested this, he found evidence to the contrary. Instead, an HIV-like virus in monkeys can infect cells throughout the entire female reproductive tract. If the same holds true for HIV in humans, it may change ideas on prevention methods.
"It's a technical achievement that provides immediate insights into the earliest transmission events," Hope said in a statement. "Now we know which areas are vulnerable to HIV and can investigate why does the virus get in here and not everywhere else?"
Hope added: "If we are going to stop women from getting infected, we have to stop the very first cells from getting infected. 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."
In the journal Cell, Host and Microbe, Hope describes tracking the virus' pathway by inserting the luciferase gene from fireflies and another that makes fluorescent proteins into the simian immunodeficiency virus (SIV).
When modified SIV was introduced to the vaginas of uninfected rhesus macaques, newly infected cells glowed. The weak point turned out to be Th17 cells, which normally serve as a first line of defense against intruders, but is depleted by both HIV and SIV. Previous studies have raised several alternative possible entry points, but Hope argues these represent cells that only become vulnerable after the Th17 cells have been breached first.
Rhesus macaques are infected with a virus very similar to HIV, making them very useful research models. Fotocon/Shutterstock
Within 48 hours, clusters of infected cells could be seen throughout the reproductive tract, and most of these were identified as likely being Th17 cells. "We can see infected dead cells, infected cells being eaten by other cells to control them, and cells that kill themselves (apoptosis)," Hope said. "The virus is causing all those things, and it shows the battle between the virus and infected host begins immediately upon infection."
Hope said that the discovery could be used to design vaccines that would “be in the right place at the right time,” rather than trying to combat infection after the virus was already multiplying.