Virogical Synapses and HIV Transmission
A new article at MIT's Technology Review highlights a recent paper about the way HIV is transmitted between CD4 T cells. Using a GFP-expressing virus, the authors ( show direct cell-to-cell transmission of HIV via formation of what's known as the virological synapse. Check it out at http://www.technologyreview.com/blog/editors/23244/
Mini Introduction to the topic:
Viruses (as well as bacteria) can infect cells in a variety of ways. Normally, we think of the route of entry as being mediated by cell surface receptors. The virus attaches to the cell through this method and is taken into the cell, where it begins to replicate itself. Later, the cell bursts, spilling thousands of viral progeny into the host; alternatively, the virus can continually bud off from the plasma membrane. (The virus can either do this right away or form a latent infection, where viral DNA is present but little viral protein is made. In this method, the virus rides along with the cell until conditions are right to start producing viruses again.)
The key point here is that at some point in their lifetime, viruses are thought to go extracellular; viral particles have to spread out and infect cells. And when they're out in the open like that, the host immune system can see them better; more arms are available to fight the virus. For example, a virus can be neutralized by antibody or a lipid envelope can be degraded by complement (to name only a few things). If a virus wasn't exposed to this arm at all, the immune system is at a disadvantage.
Relatively recent work has proposed the existence of a virological synapse which effectively transmits virus between cells without progeny having to ever enter the extracellular space. Essentially, the virological synapse is an immune synapse (in this instance, without the priming stage). MHC II, as well as adhesion molecules, are upregulated upon T cell activation. The adhesion molecules attach to other T cells and MHC II interacts with TCR, collectively forming a tight seal between T cells. Usually, this is good for T cell priming, in addition to probably playing a pertinent role in cytotoxic T cell ability.
However, CD4 T cells are a main target for human immunodefiency virus (HIV). Instead of a protective immunological synapse forming, infected CD4 T cells interacting tightly with uninfected CD4 T cells can pass on the virus through the immunological/virological synapse. This might happen a variety of ways (i.e. trogocytosis, active infection, etc) but the thing to keep in mind is, again, that this exchange is thought to keep out antibody and other effector molecules. Incidentally, if the immunological/virological synapse is presenting cognate antigen, it will help to activate (or keep activated) the uninfected CD4 T cell, which provides an excellent environment for the virus to replicate in.
Not having read the paper (sorry to so uninformed, more pressing papers to read), I don't know whether the authors prove this beyond a doubt. (For example, notice how long it takes for the uninfected CD4 T cell to become infected. Usually an infection is quicker- maybe there was virus in the supernatant that was the cause of the late GFP explosion in that CD4 T cell.) But regardless, it certainly strengthens the argument for a virological synpase and is another avenue scientists have to explore if we are ever going to effectively combat this virus.
It’d also be interesting if they took a look at FAS/FASL on these cells. If they are going to interact that strongly, what happens when activation-induced cell death (AICD) starts to really get going? (…Or does HIV inhibit this, I just don’t know.)
The actual paper can be found at:
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