Using a $225,000 microscope, researchers have identified the key components of a protein called TRIM5? that destroys HIV in rhesus monkeys.
The finding could lead to new TRIM5?-based treatments that would knock out HIV in humans, said senior researcher Edward M. Campbell.
In 2004, other researchers reported that TRIM5? protects rhesus monkeys from HIV. The TRIM5? protein first latches on to a HIV virus, then other TRIM5? proteins gang up and destroy the virus.
Humans also have TRIM5?, but while the human version of TRIM5? protects against some viruses, it does not protect against HIV.
Researchers hope to turn TRIM5? into an effective therapeutic agent. But first they need to identify the components in TRIM5? that enable the protein to destroy viruses. “Scientists have been trying to develop antiviral therapies for only about 75 years,” Campbell said. “Evolution has been playing this game for millions of years, and it has identified a point of intervention that we still know very little about.”
TRIM5? consists of nearly 500 amino acid subunits. Loyola researchers have identified six 6 individual amino acids, located in a previously little-studied region of the TRIM5? protein, that are critical in the ability of the protein to inhibit viral infection. When these amino acids were altered in human cells, TRIM5? lost its ability to block HIV-1 infection. (The research was done on cell cultures; no rhesus monkeys were used in the study.)
By continuing to narrow their search, researchers hope to identify an amino acid, or combination of amino acids, that enable TRIM5? to destroy HIV. Once these critical amino acids are identified, it might be possible to genetically engineer TRIM5? to make it more effective in humans. Moreover, a better understanding of the underlying mechanism of action might enable the development of drugs that mimic TRIM5? action, Campbell said.
In their research, scientists used Loyola’s wide-field “deconvolution” microscope to observe how the amino acids they identified altered the behavior of TRIM5?. They attached fluorescent proteins to TRIM5? to, in effect, make it glow. In current studies, researchers are fluorescently labeling individual HIV viruses and measuring the microscopic interactions between HIV and TRIM5?.
References:
1. Edward M. Campbell, et al. Identification of residues within the L2 region of rhesus TRIM5? that are required for retroviral restriction and cytoplasmic body localization. Virology, Volume 405, Issue 1, 15 September 2010, Pages 259-266. doi:10.1016/j.virol.2010.06.015
