Cold Sores: A Complete Annoyance

Have you ever had a cold sore/fever blister? If you have, then you know how painful and annoying they can be. Cold sores consist of small blisters on and/or around the lips. The area is usually red, sore and even itchy. They usually heal within a few days, and there are many medications available that speed up the healing process.

Cold sores are caused by the herpes simplex virus 1 (HSV1). Once infected, the virus remains dormant in the body until it is triggered by a stressor, such as stress, fatigue, excessive sunlight, or a weakened immune system. Cold sores are very common, for approximately 80 % of the U.S. population has been exposed to this virus. I’ve always wondered why some of us consistently have cold sores while others never get them. Those lucky people have an immune system that is able to suppress the virus.

I and other cold-sore sufferers would love it if we never had to deal with another cold sore.  Researchers at Duke University may just make this a reality one day.  They have determined how the virus remains hidden. They now understand how the virus switches from the latent phase to the active phase on a molecular level. Using this information, they may be able to reawaken the virus and kill it.

For example, while HSV1 remains dormant, it produces latency associated transcript RNA, or LAT RNA. By using mice, the research team demonstrated that the LAT RNA, extremely unstable, broke down into smaller strands called microRNAs. The microRNAs impede viral reproduction by blocking the synthesis of proteins that aid in the viral replication cycle. Therefore, the virus is able to remain dormant if there are enough microRNAs to suppress protein production. However, when a stressor is present, the virus produces messenger RNA at an amount that the microRNAs cannot block. Thus, the proteins are created and active viral replication proceeds.

Curing the occurrence of cold sores requires a combination therapy. Treatment cannot reach the virus while it is inactive, so it must be activated to kill it. The researchers have designed a drug that binds to the microRNAs responsible for keeping the virus dormant. If the drug works like they expect, it will activate the virus, which would then replicate. After activating the virus, the patient would take acyclovir, which is an antiviral medication that destroys replicating HSV1. This would result in the person being cured of cold sores. Animal trials are being used to determine how the drug can be most effectively delivered. 


It has been years since this discovery, but as we know science takes time. I will definitely keep up with the progression of this research. I hope one day we will find out that no one will ever have to deal with a cold sore again.

References:

http://www.webmd.com/skin-problems-and-treatments/tc/cold-sores-topic-overview#1

https://www.sciencedaily.com/releases/2008/07/080702132213.htm

http://esciencenews.com/articles/2008/07/02/discovery.explains.how.cold.sore.virus.hides.during.inactive.phase

https://www.herpes-coldsores.com/cold_sores.htm

A New Therapy to Combat Drug-Resistant Bacteria

Antibiotics, also referred to as antimicrobial drugs, are one of the most frequently used drugs in medicine. They treat bacterial infections by either killing the bacteria or preventing the bacteria from reproducing and spreading. The emergence of drug-resistant bacteria has reduced the effectiveness of antibiotics. It is projected that approximately 10 million people will die by the year 2050 due to drug-resistant bacteria. Therefore, it is extremely important that new methods are produced to successfully treat bacteria that has adapted over time to resist antibiotics. The researchers suggest that antimicrobial peptides (AMPs) could be a good substitute for current antibiotics. These peptides are present in all living organisms and help defend against microbial infections. Approximately half of the amino acids present in AMPs are hydrophobic, but can adopt amphipathic structures (molecules containing hydrophobic and hydrophilic regions), which allows them to penetrate cell membranes. Franco et. al generated a synthetic peptide known as clavanin-MO. A marine tunicate antimicrobial peptide was used to derive this synthetic peptide.

            Their experiments, which were performed in vitro and in vivo, showed that clavanin-MO contained antimicrobial and immunomodulatory properties. The peptide was successfully active against all the bacterial strains that were tested. Additionally, its efficacy for killing gram-negative and gram-positive bacteria was investigated, and it produced more successful results than the human cathelicidin AMP-LL37. The effectiveness of the peptide was also compared to two commonly used antibiotics, gentamicin and imipenem. Clavinin-MO proved to be more effective, even for multidrug resistant E. coli 2101123. These results exhibit clavanin-MO’s ability to treat a wide range of infections.

            The researchers also performed studies in vitro and in vivo to assess the toxic effects of clavanin-MO. Mouse red blood cells (mRBCs), RAW264.7 macrophage, L929 mouse fibroblast cell lines, and human embryonic kidney cells 293 (HEK-293) were used to perform the experiments. Concentrations of clavanin-MO necessary to produce antimicrobial activity were introduced to RAW264.7, L929 cells, and HEK-293 cells, and no cytotoxic effects were observed. A dose five times the amount necessary for successful antimicrobial treatment was administered to the mice, and still no toxicity was observed. Side effects must be considered when creating new treatments. It is very encouraging that such a large dose did not produce toxic effects. This demonstrates that the treatment can be not only effective, but also safe, which is just as important.

            Clavanin-MO was also found to contain beneficial immunomodulatory properties. One experiment was performed in vivo using the mice to track the migration of leukocytes to the infected area. A major component of treating infections involves inducing leukocytes to travel to the area of infection. Some peptides are able to perform this immunomodulatory activity. The results showed that clavanin-MO significantly increased the number of leukocytes present in the infected area of the mice.

            The increase in antibiotic-resistant bacteria coupled with the lack of antimicrobial therapy development has caused an urgency to create alternative treatments for bacterial infections. Franco et. al have introduced a possible alternative that is very promising. A single peptide, clavanin-MO, has the ability to kill bacteria directly, but can also stimulate immune cells to attack the host. Additionally, throughout the treatment process, the peptide failed to produce toxic effects. While more research is needed, this new therapy moves us considerably closer to a method that combats the rise of antibiotic-resistant bacteria.

References:

http://www.nature.com/articles/srep35465

http://www.cdc.gov/drugresistance/index.html

MutChromSeq: A New Technique for Fast Isolation of Genes

           With the ever-growing human population, it is important to produce enough food to meet the demand. The main source of food production is crops; therefore, it is vital that plants have high yields. Wheat and barley are two major crops found worldwide because they can survive in various environments, result in high yields, and contain many nutrients. If these traits could be controlled, then the yields would increase and there would be food security on a global scale. To control these traits, we must know the genes responsible for them. All we need to do is locate these genes in wheat and barley. This is easier said than done. Wheat and barley have large genomes and large regions of suppressed recombination. This makes it very time-consuming and expensive to use traditional map-based gene isolation. Additionally, obtaining sequences of whole genomes from several mutants is not feasible because comparing large datasets is challenging and costly. There are multiple techniques that can be used to make the sequences of the wheat and barley genomes less complex. However, these methods often result in some sequences being overlooked. Wulff et. al developed a new technique to reduce the complexity of the wheat and barley genomes that does not overlook certain sequences.

Their technique, MutChromSeq, involves flow sorting and comparing the sequences of various mutant chromosomes. This method identifies the mutation and eliminates the need for fine mapping and recombination. MutChromSeq was used to reclone the barley Eceriferum-q gene and clone de novo the wheat Pm2 gene. Even though a false positive was included in the Eceriferum-q example, the correct gene was still identified. The chromosomes were isolated using fluorescent markers. The sequences of the six mutant chromosomes were compared to the wild-type chromosomes.

This approach includes mutagenesis, the reduction of genome complexity, and high-throughput screening. Therefore, the plant species must be able to undergo mutagenesis. Also, the phenotype of the target gene and the chromosome the gene is on must be known. MutChromSeq can be used on genes that meet these requirements, and the method is quick and inexpensive. This method makes it possible to isolate and clone genes that were very difficult to manage in the past.

The researchers introduce a very powerful technique for gene isolation. For genes that could not be easily cloned before, there is now a fast and inexpensive technique that can be used. This is especially impactful for the production of crops. With this new approach, the genes that produce beneficial traits in crops can be targeted. Thus, crops can be improved to better withstand pests and changes in weather. This is very encouraging for the future of food production.

Reference:

Javier Sánchez-Martín, Burkhard Steuernagel, Sreya Ghosh, Gerhard Herren, Severine Hurni, Nikolai Adamski, Jan Vrána, Marie Kubaláková, Simon G. Krattinger, Thomas Wicker, Jaroslav Doležel, Beat Keller, Brande B. H. Wulff. “Rapid gene isolation in barley and wheat by mutant chromosome sequencing.” Genome Biology, 2016.

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1082-1