Dengue and my research on host factors

NPR reports that Dengue outbreaks spread to the Southern reaches of the United States. This is an issue that is close to my heart as I spend my days studying how Dengue infects humans and carries out its lifecycle.

Dengue is important and you should know about it because it infects hundreds of millions of people a year. This is equivalent in its range and severity to American Idol which also causes tens of thousands of people to develop debilitating headaches and delirium. Before Dengue virus kills you, or maybe instead of killing you, it makes you bleed profusely in a socalled Hemorrhagic fever. It also causes joint pain, fever, chills and muscle pain so severe they call it "breakbone fever".

The virus is a close cousin to Hepatitis C. It is composed of RNA (similar to DNA) and a three proteins. This is a bit less biologically sophisticated than most enzymes except that it is self replicating and does so by taking advantage of host proteins. This is where I come in. I study which host proteins the virus uses and how it uses them. As a genetic pauper carrying only nine genes of its own, Dengue virus has to steal host proteins to reproduce its genes, makes its protein shell, make its enzymes and assemble itself.

Part of what makes this virus a major public health concern is that it exists as a "quasispecies". That is, there is a large amount of heterogeneity in natural isolates of the virus. Our immune system is really good at reacting to something but if it looks slightly different, structurally speaking, the immune system doesn't react very well to it. Herein lies a huge problem- antibody dependent enhancement. This is a phenomenon where antibodies, the immune system's sticky proteins that help it kill invaders by showing immune cells what to eat and digest, fail to prevent the virus from moving around and carrying out its business. So the virus gets coated in antibodies that don't immobilize it and gets eaten by immune cells that fail to kill it. The virus reproduces itself in the immune cells and eventually spreads in the blood to the liver. Multiple subtypes of Dengue exist which produce different antibodies in their host and if you have had one subtype, you are more likely to have a severe reaction to another.

The virus is spread by mosquitoes from infected person to infected person. The virus infects the salivary glands of the mosquito as well as human immune cells, human liver cells and even cells from other animals. If you think about how different these types of cells really are (and they are really really different) you can appreciate how resilient this virus actually is in its ability to infect. Since there is no vaccine or cure for Dengue fever, once you get it you are boned. The best approaches to control Dengue focus on controlling the mosquito populations.