Gene Can Block The Spread Of HIV
A team of researchers at the University of Alberta has discovered a gene that is able to block HIV, and in turn prevent the onset of AIDS. Stephen Barr, a molecular virologist in the Department of Medical Microbiology and Immunology, says his team has identified a gene called TRIM22 that can block HIV infection in a cell culture by preventing the assembly of the virus.
“When we put this gene in cells, it prevents the assembly of the HIV virus,” said Barr, a postdoctoral fellow. “This means the virus cannot get out of the cells to infect other cells, thereby blocking the spread of the virus.”
Barr and his team also prevented cells from turning on TRIM22 – provoking an interesting phenomenon: the normal response of interferon, a protein that co-ordinates attacks against viral infections, became useless at blocking HIV infection.
“This means that TRIM22 is an essential part of our body’s ability to fight off HIV. The results are very exciting because they show that our bodies have a gene that is capable of stopping the spread of HIV.”
One of the greatest challenges in battling HIV is the virus’ ability to mutate and evade medications. Antiretroviral drugs introduced during the late 1990s interfere with HIV’s ability to produce new copies of itself – and even they are beneficial, the drugs are unable to eradicate the virus. Barr and his team have discovered a gene that could potentially do the job naturally.
“There are always newly emerging drug-resistant strains of HIV so the push has been to develop more natural means of blocking the virus. The discovery of this gene, which is natural in our cells, might provide a different avenue,” said Barr. “The gene prevents the assembly of the virus so in the future the idea would be to develop drugs or vaccines that can mimic the effects of this gene.”
“We are currently trying to figure out why this gene does not work in people infected with HIV and if there is a way to turn this gene on in those individuals,” he added. “We hope that our research will lead to the design of new drugs, or vaccines that can halt the person-to-person transmission of HIV and the spread of the virus in the body, thereby blocking the onset of AIDS.”
The researchers are now investigating the gene’s ability to battle other viruses.
The Interferon Response Inhibits HIV Particle Production by Induction of TRIM22.
Barr SD, Smiley JR, Bushman FD (2008)
Treatment of human cells with Type 1 interferons restricts HIV replication. Here we report that the tripartite motif protein TRIM22 is a key mediator. We used transcriptional profiling to identify cellular genes that were induced by interferon treatment and identified TRIM22 as one of the most strongly up-regulated genes. We confirmed, as in previous studies, that TRIM22 over-expression inhibited HIV replication. To assess the role of TRIM22 expressed under natural inducing conditions, we compared the effects of interferon in cells depleted for TRIM22 using RNAi and found that HIV particle release was significantly increased in the knockdown, implying that TRIM22 acts as a natural antiviral effector. Further studies showed that TRIM22 inhibited budding of virus-like particles containing Gag only, indicating that Gag was the target of TRIM22. TRIM22 did not block the release of MLV or EIAV Gag particles. Inhibition was associated with diffuse cytoplasmic staining of HIV Gag rather than accumulation at the plasma membrane, suggesting TRIM22 disrupts proper trafficking. Mutational analyses of TRIM22 showed that the catalytic amino acids Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity. These data disclose a pathway by which Type 1 interferons obstruct HIV replication.