Human immunodeficiency virus type-1 (HIV-1) is known to cause AIDS, but the precise way it does this may not be known. In an attempt to enhance the knowledge on this mechanism, scientists from The Children’s Hospital of Philadelphia claim to have found the way an HIV protein helps the virus to become reactive after entering a dormant state by hiding in cells. Understanding the biological events that revive HIV from latency can supposedly open doors to better treatments for people diagnosed with HIV infection.
Viral latency probably is one of the persistent problems in treating HIV infection. Currently available combinations of anti-HIV drugs allegedly decrease HIV to undetectable levels, but the virus hides within latently infected cells in a sort of hibernation. Once the intake of medications is stopped or weakened by a different infection, HIV seemingly comes back becoming resistant to previously effective drugs. In this research, experts aimed to examine a protein, Vif (for viral infectivity factor), that is believed to be produced by HIV-1.
“If we can interrupt the activity of Brd4 or Cdk9, we may be able to prevent latent infection from becoming active,” said research leader Terri H. Finkel, MD, PhD, chief of Rheumatology at The Children’s Hospital of Philadelphia. “Alternatively, by harnessing Brd4 or Cdk9, we may be able to drive cells out of latency and make the virus susceptible to anti-HIV drugs.”
This protein was initially assumed to halt the growth at one phase of the cell cycle, also known as the G2 phase. However, now it was pointed out that Vif may also act in an earlier stage of cell cycle, driving cells out of the G1 phase and into the more active S phase. This activity appears vital as G1 is a resting phase, and a biological interaction that ‘wakes up’ a latent infected cell and reactivates the infection.
The other viruses that also seem to have a latent infectious state include the herpes virus and the Epstein-Barr virus that drive a transition from G1 to S phase. The research was conducted on HeLa cells that are found in the blood. Two proteins, Brd4 and Cdk9 were supposedly interacting with Vif and can therefore serve as a potential target for therapy. Further investigations are being initiated to lay hands on clinical treatments for HIV.
The research was published in the January 27 issue of the journal Blood.