U research focuses on retroviruses

New findings clarify aspects of retrovirus replication and could advance anti-HIV drug creation.

Keaton Schmitt

After almost a decade of research, experts at the University of Minnesota found that a retrovirus similar to HIV acts differently than previously thought, which could enable the creation of more effective anti-HIV drugs.
 
 
According to University research published last week in the science journal Nature, the Rous sarcoma virus forces host cells to copy with “claws” made of eight molecules — twice the number scientists had previously predicted. The finding suggests drugs that target these claws could be made to fight related viruses like HIV.
 
 
A retrovirus is different from a normal virus because it directly inserts DNA into a host’s genetic information, said Hideki Aihara, co-author on the study and University professor.
 
 
Integrase, the molecule that makes up the claws in RSV, isn’t found in host cells. 
 
 
Researchers could theoretically make a drug to target it and stop the virus without harming human cells, said Aihara.
 
 
Until this study, biochemists thought HIV and other retroviruses had just four integrase copies, because of previous studies with a virus less similar to HIV than RSV, he 
said. 
 
 
“For HIV and other viral systems, we had this rough idea of how it would do the job. … Basically, it looked very different [from what was expected],” said Aihara
 
 
The discovery adds insight into how RSV acts, he said, because on a small scale the difference of a few molecules can change how integrase behaves.
 
 
This news could also help researchers understand how HIV infects host cells, Aihara said.
 
 
“Now that we have this RSV structure, probably we can predict how HIV integrase functions,” said Aihara.
 
 
The team crystallized the virus and hit it with rays in a process called X-ray diffraction, said Surajit Banerjee, study co-author from Cornell University who measured the scattered rays.
 
 
When a ray hits a molecule, it scatters, and when researchers measure the scattering, they can figure out the structure of the molecules, said Banerjee.
 
 
He said he gathered data at a multi-university lab with advanced facilities to show the structure more clearly.
 
 
“With this resolution, we can explain all the atomic details,” Banerjee said.
 
 
Zhiqi Yin, a University of Minnesota researcher and co-author on the study, said the team has worked on this project since 2008 but first had success in 2011 when he joined the team and they started to use a new approach.
 
 
Now that they’ve found the structure of RSV, the researchers plan to map the structure of HIV, he said.
 
 
“Ultimately, if you really want to develop the best structure-based drug, we need to have a high resolution structure of HIV-1,” said Aihara.