Wednesday, June 3, 2015

A New Way to Look at Viruses—Weighing by Mass Spectrometry

            There are various techniques that have been used over the years to study viruses. Scientists have studied their pathological effects in living systems, their cytopathic effects in cell culture. We can directly observe viruses through x-ray crystallography.

Pathological Approach:
 Varicella-zoster virus is one of a myriad of viruses that causes distinctive signs and symptoms/pathologies. The body’s immune response to the varicella-zoster virus causes the characteristic red spots of chickenpox. The list goes on. Macroscopic diagnoses can be used in epidemiological studies and for diagnostic purposes. Before the development of modern laboratory and imaging techniques, this was how many viral illnesses were first characterized.

Cytopathic Effect:
Characteristic deformities that certain viruses cause to the cells they infect. For example, some herpes viruses cause multinucleation. Respiratory syncytia virus (Paramyxoviridae) causes syncytia (fusion of multiple cells into one large one).

--multinucleation (wikimedia commons)

X-Ray Crystallography:
Was used to produce the first pictures of DNA--it involves studying the diffractions of x-rays from crystalline atoms.

--X-ray crystallography of Poliovirus type 1

Scanning Electron Microscopy:

Scanning electron microscopes produce 3-dimensional images. They can show topographical details of a virus.


Transmission Electron Microscopy:

TEM has a higher magnification and greater resolution, but produces 2-dimensional rather than 3-dimensional images.

However, there has just been a study to use a different imaging technique to study viruses: mass spectrometry. For the first time ever, we can weigh an intact virus. Specifically, the study used heavy-ion mass spectrometry MS to study a mixture of intact virus particles. The team, led by Carnegie Mellon University’s Mark Bier and his graduate student Logan Plath, used samples containing two varieties of a cowpea (black-eyed pea) mosaic virus (a plant virus); they found that one virus weighted 5.65 megadaltons, and the other 4.84 megadaltons. Both of these numbers were approximately that of the theorized masses of the viruses.
Previously, mass spectrometry’s use in virology has been limited because intact viruses have been too large. To get around this problem, Bier’s group used a cryodetector-based matrix-assisted laser desorption/ionization time of flight mass spectrometer (that’s a real mouthful), called a Macromizer. The 3.75 meter-long apparatus can analyze low charge heavy ions with greater sensitivity than standard mass spectrometers.

--black-eyed pea mosaic virus--what's it gonna do with all those megadaltons inside that trunk?


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