Monday Micro – killer viruses

By Siouxsie Wiles 03/02/2014

Recent virus-related papers to get excited about:

1. Visualising HIV infection

A paper just out in the open access journal PLOS Pathogens describes using 3D electron microscopy to visualise the Human Immune Immunodeficiency Virus (HIV)-1 infecting gut immune cells (1). If you remember, HIV is the virus which causes acquired immunodeficiency syndrome (AIDS). It’s believed that 33 million people worldwide are infected with HIV.

Until reading this paper, I hadn’t realised that gut mucosal tissues were involved in HIV infection. According to the researchers, the gut contains large numbers of target cells which become depleted early on in HIV infection. Ladinsky and colleagues wanted to look at where the virus goes during an active infection so they needed to use some nifty tricks to make that possible. The first was to make mice which contain immune cells that HIV can infect. As the virus is pretty specialised for infecting human cells, it doesn’t normally infect mice. The researchers grafted mice with human immune cells, and then a few months later injected the mice with HIV. Mice were then euthanised and gut tissues removed and fixed for looking at using a fancy microscope. And here’s an example of a reconstructed image where the modelled virus particles are shown in blue. Pretty!

Tomographic slice of gut immune cells with modelled HIV virions (blue, membrane; purple, cores; average diameter = 99.3+/−4.7 nm). Adapted from ref 1

2. Hijacking the bacterial ‘immune system’ to make smart antibiotics

I’ve written before about the fact that bacteria can become infected with viruses, called phage. The bacteria have developed numerous forms of ‘immunity’ to protect themselves from attack, including the CRISPR system, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. In this quite elegant system, foreign genetic material is chopped up and incorporated into the bacterial genome (as ‘spacers’) between CRISPR repeats. These spacers then serve as a sort of immune ‘memory’ of past potential invaders. Upon re-exposure, the CRISPR spacers recognise the foreign genetic material and target it for destruction.

In a paper just published in the open access journal mBIO, Gomaa and colleagues have shown that this CRISPR-Cas system can be hijacked to kill specific strains of bacteria (2). They designed and administered specific CRISPR spacers into mixed cultures of bacteria and showed that they could kill the particular bacterial strain they were targeting. This is exciting as one of the problems with current antibiotics is that they kill good and bad bacteria in one sweep. Now the researchers have to figure out CRISPR spacers could be delivered to target bacteria during an infection. Watch this space.

3. Exploiting viruses to target cancer cells for destruction.

And finally, a paper just published in the FASEB Journal describes using an engineered vaccinia virus to target breast cancer cells for destruction (3). Gholami and colleagues engineered vaccinia virus to carry the gene encoding the human sodium iodide symporter (hNIS). When the virus infected breast cancer cells, it made the cells produce hNIS. What’s cool about this is that hNIS is the protein that normally concentrates iodine in thyroid cells. By grafting the engineered tumour cells into mice, the researchers were able to treat the tumours by giving the mice radioactive iodine, a form of radiotherapy used to treat thyroid cancer in humans. Clever.

1. Ladinsky MS, Kieffer C, Olson G, Deruaz M, Vrbanac V, et al. (2014) Electron Tomography of HIV-1 Infection in Gut-Associated Lymphoid Tissue. PLoS Pathog 10(1): e1003899. doi:10.1371/journal.ppat.1003899

2. A. A. Gomaa, H. E. Klumpe, M. L. Luo, K. Selle, R. Barrangou, C. L. Beisel. Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems. mBio, 2014; 5 (1): e00928-13 DOI: 10.1128/mBio.00928-13

3. S. Gholami, C.-H. Chen, E. Lou, L. J. Belin, S. Fujisawa, V. A. Longo, N. G. Chen, M. Gonen, P. B. Zanzonico, A. A. Szalay, Y. Fong. Vaccinia virus GLV-1h153 in combination with 131I shows increased efficiency in treating triple-negative breast cancer. The FASEB Journal, 2013; 28 (2): 676 DOI: 10.1096/fj.13-237222