In an unexpected twist, a family of proteins that have been found to promote HIV-1 entry into cells also potently block viral release. Interestingly, these proteins were also found to inhibit the release of other viruses, including Ebola virus. These intriguing new findings provide us with novel insights into both viral infection and the development of AIDS, which could ultimately lead to new antiviral strategies. The study has been published in Proceedings of the National Academy of Sciences.
Viruses are unable to replicate by themselves and thus must hijack a host cell’s machinery in order to do so. To get inside host cells, HIV, or human immunodeficiency virus, needs to bind to receptors found on target cells. This triggers a series of events that ultimately lead to viral entry; once inside, HIV converts the cell into a factory for making more viruses.
Recent studies have identified a family of proteins, called TIM proteins, which play critical roles in facilitating the entry of various viruses including Ebola, West Nile and dengue viruses. Intriguingly, University of Missouri researchers have now discovered that these proteins not only promote HIV-1 entry into host cells, but they also prevent viral release.
For the study, scientists investigated the interactions between HIV-1 and TIM proteins using various molecular, biochemical and microscopic techniques. They found that as HIV-1 begins to bud from, or escape, the host cell, TIM proteins become incorporated into the virions and tether the particles to the cellular membrane. This is mediated through interactions with a lipid called phosphatidylserine (PS) that is found both on the cell membrane and the outside of the virus particles. Usually, PS is expressed on the inside of the cell, but viral infection causes it to flip to the outside, meaning that both PS and TIM are now present on the cell and viral surface. TIM and PS then bind to one another as HIV-1 attempts to escape from the cell, causing the particles to be retained at the cell surface.
Interestingly, the team also discovered that TIM proteins inhibited the release of other viruses including a mouse virus belonging to the same family as HIV (murine leukemia virus), and also Ebola virus.
While these discoveries extend our understanding of viral infection, lead researcher Shan-Lu Liu points out that it is not clear at this stage whether HIV’s interaction with TIM proteins is a positive or negative factor. “However, this discovery furthers our ultimate goal of understanding the biology of TIM-family proteins and potentially developing applications for future antivirus therapies,” he says.
[Header image "Illustration of Human Immunodeficiency Virus" from Visual Science]