HIV is far and away one of the most studied diseases ever, yet we continue to learn new things about the virus itself and how the human body interacts with it. The most recent discoveries are proteins in the blood and within specialized immune cells that appear to kill the virus.
These findings may help to explain why it is relatively difficult to become infected with HIV compared with many other viruses, such as hepatitis B, which is 100 times more easily transmitted. They also suggest new ways to perhaps prevent infections and control the virus once a person does become infected.
Estimates are that more than a million different peptides and small proteins are present in blood. They are a mix of chemical signals that the body uses to communicate with itself and trash—fragments of larger molecules that have been broken up and are destined to be recycled or excreted.
A German team of researchers based at the Institute of Virology at the University of Ulm undertook the arduous task of screening this library for activity against HIV. They found several that had some activity and dubbed the most potent one Virus-Inhibitory Peptide ( VIRIP ) .
Through a complex series of experiments they learned that VIRIP binds to gp41, one of the most prominent molecular features on the surface of HIV and important to understanding how the virus enters a cell. In binding to gp41, VIRIP neutralizes the virus and prevents that entry into a cell.
VIRIP worked against strains of HIV from around the world and against strains that were resistant to existing therapies. Tweaking the atomic structure of VIRIP, the researchers were able to create a molecule that binds even more tightly to gp41; it is two orders of magnitude more potent than the natural VIRIP structure.
The researchers believe that their molecule has the potential to be a new class of drugs that blocks entry of HIV into cells. The study was published on April 20 in the prestigious journal Cell.
LANGERIN
Over the same time period, a team of researchers based in Amsterdam discovered that Langerhans cells can capture HIV through a molecule called langerin, which is on the surface of those cells, and transport the virus to a structure inside the cell where it is degraded.
Langerhans cells are a specialized part of the immune system that are commonly found in the skin and mucosal tissue such as the vagina, foreskin and rectum. Thus, they are among the first cells that HIV encounters with exposure through sex.
The langerin appears to protect against infection when the amount of HIV is relatively low, but a large amount of HIV seems to overwhelm it. The Dutch researchers also found that tissue samples from different people showed different levels of protection against infection, suggesting, not surprisingly, that there is a genetic component to langerin. The paper was published in Nature Medicine.
It may be possible to develop a topical microbicide for use in the vagina or rectum that will stimulate additional production of langerin to help protect against the transmission of HIV. But that will take years of additional work and perhaps a bite of luck.
