Author: Ria Foye-Edwards
Institution: Syracuse University
Ria Foye-Edwards is a senior at Syracuse University. She enjoys reading and writing about nature and working as an undergraduate researcher in a developmental biology lab under the direction of Dr. Katharine Lewis.
There are many diseases characterized by a high level of communicability and a diverse array of symptoms. One such disease, HIV-1, can sicken some infected individuals rather quickly, but in other infected individuals, the symptoms can occur much later. Of the two types of HIV, HIV-1 and HIV-2, HIV-1 is the most common strain and, like HIV-2, is easily transmitted through blood, sexual contact and from mother to child during childbirth. The varying onset of HIV-1 symptoms in patients has puzzled doctors for decades. Researchers at the University of Minnesota might have an explanation for the genetic variation responsible for differences in the onset of HIV-1 symptoms.
When an individual is infected with HIV-1, the virus attacks immune cells known as T lymphocytes. The virus begins replicating and spreading throughout the body, destroying the host’s cells and leaving the individual more susceptible to other diseases as a result of a weakened immune system. T lymphocytes are not completely unarmed, however, as they have a class of defense proteins called APOBEC3 that halt HIV-1’s replication machinery.
These proteins could normally stop HIV-1 from continually dividing, but unfortunately, HIV-1 is armed with its own defense proteins, called Vif, which force the host’s T lymphocytes to destroy host APOBEC3 proteins instead.
Professor Reuben Harris at the University of Minnesota’s College of Biological Sciences and doctoral student Eric Refsland at the University’s Medical School were the first to suspect that the different susceptibilities to HIV-1 were closely related to genetic variations in the APOBEC3 and Vif host genes.
One finding revealed HIV-1’s ability to boost production of APOBEC3H, a subtype of the APOBEC3 protein. This discovery suggests that APOBEC3H plays a major role in defense upon infection. Using a technique known as separation of function mutagenesis (a technique where mutations are introduced into a protein to destroy one particular biochemical property and leave the other properties of the protein intact), the team made another critical discovery: different individuals express various levels of stable and unstable APOBEC3H.
Those individuals with stable levels of APOBEC3H were able to repress HIV-1’s ability to continually divide only if the virus had weak levels of Vif proteins, but not for those with stronger Vif proteins.
Given this newfound relationship between APOBEC3 and Vif proteins, researchers have a clearer image of how to develop a defense mechanism and stop HIV-1 replication.
Harris said in a press release, “One could imagine drugs that stop Vif from binding with APOBEC...This is a bonafide HIV killing pathway, and we just have to devise clever ways to activate it in infected persons.”
This News Brief was produced under the guidance of Science Writing Mentor Susan Swanberg.