Welcome to this installment of The AIDS Pandemic. I’m Dave Wessner.
Could our own bodies be producing potent inhibitors of HIV? According to research published in today’s issue of Cell, the answer may be ‘Yes.’ And these interesting findings eventually may lead to the development of new anti-retroviral drugs.
Since the isolation of HIV in 1983, numerous naturally occurring human factors have been postulated to have anti-HIV properties. Today, a group of researchers in Germany have added another factor to this list. By studying hundreds of small molecules isolated from human blood, the researchers identified a short peptide, or protein fragment, that effectively blocked HIV from infecting cells. Termed Virus-Inhibitory Peptide, or VIRIP, this peptide represents a small piece of a larger protein normally found in our blood – alpha1-anti-trypsin.
To demonstrate the inhibitory effects of VIRIP, the researchers infected cell lines with HIV-1, added VIRIP to the cells, and then determined how many additional cells subsequently became infected. VIRIP decreased the infection rate in a dose-dependent manner. In other words, when higher concentrations of VIRIP were used, the effect was greater. The effect also was very specific for HIV; the peptide did not block the infectivity of other types of viruses. Interestingly, the researchers showed that if they altered the VIRIP peptide slightly, it’s inhibitory properties increased dramatically. Finally, VIRIP was equally effective against strains of HIV that were resistant to other anti-retroviral drugs, yet resistance to VIRIP was not observed.
Mechanistically, it appears that VIRIP blocks HIV infection by binding to the viral protein gp41 and preventing fusion between the viral envelope and the cell membrane. An existing drug, T20, or Fuzeon, works in a similar manner.
The path from an initial discovery like this and a marketable drug is a long and winding path, filled with potholes. Promising candidate molecules rarely become FDA-approved drugs. So, the odds are against VIRIP. But, based on this report, it’s certainly worth keeping our eye on it.
Until next time, I’m Dave Wessner.