Herpes don’t hurt me!

Courtesy of Emneth Design

Courtesy of Emneth Design

“Don’t look at me, I’m a monster!” The herpes simplex virus (HSV) plagues many people worldwide putting them at social and more importantly physical danger as the virus can lead to mortal complications. Researchers of the University of Washington and Hutchinson Cancer Research Center found that Nelfavir can trap herpes within cells and turn it from a danger to an annoyance.

This study looked into the ways in which Nelfinavir (NFV), an anti-cancer drug, could be used to combat the virus causing herpes, specifically HSV-1. HSV is a non-living, infectious agent that looks like a durian fruit. The DNA of the virus is inside while the outside “skin” is made of protein and “spikes” are made of glycoproteins (sugar-proteins). The glycoproteins are what allow the virus to enter human cells and infect. HSV infection causes the cell to waste its resources to make new viruses that can infect other cells. With HSV comes elevated risk of aquiring HIV and Kaposi sarcoma, a cancer.

Imagine a factory that makes cars and all the machinery inside is blue. The factory can be equated to a cell. If a virus infects, this would be akin to someone adding instructions and an extra machine or two to the factory that now allows bombs to be made in the car factory. Imagine the extra machine is yellow. It is easy to spot and get rid of the extra machinery that is making bombs if it does not look like the original factory machinery. This is how most drugs target and destroy viruses. The virus machinery is often easy to differentiate from cell machinery. What if the virus machinery were also blue? This is when a virus becomes drug resistant. The virus has changed, so the drug can no longer target and destroy it. Instead of targeting the virus itself, another method of stopping viruses is by changing the cell machinery so that it will rarely make a fully functioning bomb (virus). This is how NFV acts on HSV-1.

The researchers infected human connective tissue cells, fibroblasts, with HSV-1 and treated with NFV to measure its effectiveness in blocking virus production in vitro. It was found that NFV blocked viral protein maturation, glycoprotein development, and viral packaging.

Virus retention inside the cell was 79:14, NFV treated:untreated
Virus particles found outside the cell was 3:51, NFV treated:untreated
Virus completion inside the cell was 0:9, NFV treated:untreated

This meant that although HSV-1 was getting into the cells, new viruses were created broken and could not leave or infect other cells. It was also found that HSV-1 was not becoming resistant to the drug even after subjected to drug pressure. This is because NFV affects the cell rather than virus.

This newfound use for Nelfinavir shows promise for longterm control of herpes. This ubiquitous and malignant virus may soon be just a small bother.

Soren Gantt, Eliora Gachelet, Jacquelyn Carlsson, Serge Barcy, Corey Casper, Michael Lagunoff. Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation. Advances in Virology, 2015

Stem Cells Heal Hearts

Photo courtesy of Abigail Droege

Photo courtesy of Abigail Droege

Running up stairs, hiking a new trail, eating great food can all cause acute, unexpected heart attack. That is, given arterial plaque buildup is unstable and ready to pop. Researchers of Zhejiang University, Ningbo University, and the Chinese PLA 305 Hospital, however, found that mesenchymal stem cells can stabilize this heartbreaking plaque.

Cardiovascular disease is the number one most common cause of death worldwide accounting for over 25% of all deaths in 2012. More specifically, one out of every six deaths in the United States is caused by heart attack alone. A large contributing factor to heart attack is accumulated plaque within the walls of arteries. This research focused on a big player in sudden and often unexpected heart attack, vulnerable plaque.

As cholesterol moves through the bloodstream, excess will often accumulate in the walls of blood vessels. Seen as a foreign substance, the cholesterol pool will constantly be attacked by white blood cells. This however, leads to larger plaque buildup as the macrophages and neutrophils are swallowed up by the tarlike plaque. As well, the fibrous cap keeping the plaque away from the blood thins out as cells die. Although the narrowing of arteries is dangerous, acute heart attack is only induced once the lipid deposit ruptures and spills into the bloodstream. This instantly clogs arteries.

Process of vulnerable plaque rupture and arterial blockage

Process of vulnerable plaque rupture and arterial blockage

If inflammation around the plaque could be stopped, white blood cells would not exacerbate growth, the fibrous cap would remain thick and robust, and the fatty clot would not form. The researchers experimented with stem cells’ ability to prohibit inflammation and thereby stabilize plaque deposits.

Forming groups of ten, 30 rabbits were put into either stable plaque (SP), vulnerable plaque (VP), or mesenchymal stem cell (MSC) groups. The groups had plaque formations with no danger of rupture, extreme danger of rupture, or extreme danger of rupture with the addition of MSC’s respectively. To detect plaque stability throughout the project, H&E and Masson staining were used to measure the fibrous cap/lipid core ratio. A high ratio indicated low chance of rupture (stable) while a low ratio indicated high chance of rupture (vulnerable).

After the intravenous introduction of MSC’s, levels of various inflammation markers were measured over a four week period. The following was found:

Pro-inflammatory compound levels (hs-CRP, TNF-a, IL-6, NF-kb)
MSC: Low
SP: Low
VP: High

Anti-inflammatory compound levels (TSG-6, IL-10)
MSC: High
SP: Normal
VP: Normal

As well, the levels of cellular suicide inducer MMP were found to be low in the MSC group. This meant that the stem cells were decreasing inflammation and apoptosis at the site of the plaque deposit. Vulnerable plaques with high risk of inducing abrupt heart attack were transformed into less harmful, stable plaques without the risk of causing sudden cardio-ischemic attacks.

Stem cells seem to be the next big hero of the heart. The list of accomplishments for these little multipotent warriors just keeps on growing.

Shuang-shuang Wang, Si-wang Hu, Qing-hua Zhang, Ai-xiang Xia, Zhi-xin Jiang, Xiao-min Chen. Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties. PLOS ONE, 2015