The HIV-1 virus produces various proteins needed for infection and replication in human cells. Some of these are accessory proteins that mainly help the HIV-1 virus to evade the immune system defenses and to overcome factors that function to restrict or inhibit infection. One protein that may function in this way is the Vpr protein, which is a virion (infective virus form)-associated protein.
The actual function of Vpr is not well understood due to lack of a suitable cell culture system that shows changes in HIV-1 replication when Vpr is absent. It is known that monocyte-derived dendritic cells (immune cells that process and present antigens to T cells) are among the first cells in the human body to interact with HIV-1 in tissues. Therefore, research was conducted using a new cell culture system using primary human dendritic cells. The main goal was to determine if Vpr is necessary for HIV-1 to infect monocyte-derived dendritic cells.
The researchers found that infection of the dendritic cells was inhibited at the viral transcription stage (production of mRNA that will lead to viral protein production) when infected with HIV-1 lacking Vpr. They then introduced Vpr associated with incoming\external virus particles into these cells. This external Vpr was incorporated into the Vpr-deficient virus particles at levels that are similar to those in wild type (natural form) HIV-1 virus particles. Using a luciferase expression assay to observe gene expression at the transcription level, they found that dendritic cell infection was again possible using the incorporated Vpr.
These results suggest that external virion-associated Vpr can overcome dendritic cell factors that block early steps in the HIV-1 replication process. The reduction in viral replication in monocyte-derived dendritic cells infected with Vpr-deficient HIV-1 provides a novel cell culture system that facilitates a better understanding of the importance of Vpr in HIV-1 infection. Knowledge regarding how Vpr overcomes dendritic-cell control of HIV-1 viral infection can provide valuable information needed to develop new therapies for HIV-1 infection.
Miller, C., Akiyama, H., Agosto, L., Emery, A., Ettinger, C., & Swamstrom, R. et al. (2017). Virion associated Vpr alleviates a post-integration block to HIV-1 infection of dendritic cells. Journal Of Virology, JVI.00051-17. doi:10.1128/jvi.00051-17