Friday, May 3, 2013

Drug Resistant HSV, Soon not to be a Problem!


Herpes is nothing new to society and has been a constant nuisance for many years. But a recent article published by the Proceedings of the National Academy of Sciences claims that they have engineered a mutant antibody that is able to effectively neutralize HSV and drug resistant HSV…in mice. Granted not the best news in the world but hey it’s a start!

Before that, a little bit more about the Herpes virus. The Herpes virus can be broken up into two types, HSV-1 which normally causes oral sores and HSV-2, which usually affects the genital region.  Herpes is an enveloped, double strand DNA virus, that is particularly good at causing long-term infection, or latent infections. Once it enters the body it usually persists for the remainder of ones lifetime, with the possibility of the infection becoming active from time to time. Studies show that usually a very minimal amount of people, with a functioning immune system, reactivate the virus, than those who are immunocomprised.

Various antiviral drugs have been developed and have been shown to decrease virus reactivity, such as Acyclovir. However, as attributed to many viruses, they become drug resistant. This drug resistance is particularly seen in individuals with compromised immune systems, and a better treatment for them is continually being researched. Thus we arrive at what the researchers did!

Although still in its early trials, researchers have engineered an antibody known as mAb hu2c. The antibody works by negating the mechanism through which HSV is able to spread from cell to cell. This is a huge step in defeating the virus, being that HSV is able to successfully avoid the immune system through the cell-to-cell spread mechanism. A quick summary of this mechanism: most viruses infect target cells by releasing virions that ultimately infect target cells. In order for this to occur the virus has to face the extracellular environment and in doing so triggers an immune response. Cell-to-cell spread is a mechanism in which a virus can infect other surrounding cells without ever having to face the extracellular environment, and thus can essentially be “hidden” from our immune system. HSV’s ability to cause infection from cell to cell is mediated by viral glycoproteins.

The result of the affinity and neutralization capacity of the antibody was significant. The researchers injected the mAb hu2c antibody into HSV infected mice, and measured affinity to the glycoprotein and the neutralization ability.   The researchers have shown that the epitope, glycoprotein-binding site, on the viral protein has a high affinity for the binding of the antibody, mAb hu2c. With a high affinity for binding to the glycoprotein, as well as showing successful neutralization and aboration of cell-to-cell spread, this verified that the murine (mouse) based antibody could be a framework for engineering a similar human antibody! And guess what, they did it!

The article reports that researchers engineered a human form of the mouse antibody mAb hu2c. This new human antibody has also been tested in human cells in vitro and in vivo. The results were incredible; the human form of the antibody showed, like its murine counterpart, high affinity to the glycoprotein epitope as well as high neutralizing capacity. Furthermore the antibody even showed that it was effective in preventing the mice from HSV onset. The biggest result was the ability for the antibody to successively neutralize known drug resilient HSV virus strains. THIS IS HUGE!

Viruses becoming drug resistant are one of the main issues that drug developers face. The ability for this antibody to target drug resistant HSV as well as preventing HSV infection is a major stepping-stone in developing not only a successful treatment for HSV resistant individuals but also the possibility of creating a vaccine that can prevent the virus from the beginning. Furthermore, certain drugs used to treat HSV, such as DNA polymerase inhibitors, drugs that prevent the genomic replication of the virus, are usually toxic to the individual. As part of the researchers experiment, the human mAb hu2c antibody showed no major side effects, which furthers the importance of clinical trials and further data into validating these findings!

Primary Article:

Adalbert Krawczyk, Michaela A. E. Arndt, Ludger Grosse-Hovest, Wilko Weichert, Bernd 
Giebel, Ulf Dittmer, Hartmut Hengel, Dirk Jäger, Karl E. Schneweis, Anna M. Eis-Hübinger, 
Michael Roggendorf, and Jürgen Krauss 
Overcoming drug-resistant herpes simplex virus (HSV) infection by a humanized 
PNAS 2013 110: 6760-6765.

Secondary Article:

Remeijer L, Osterhaus A, Verjans G.
Human Herpes Simplex Virus Keratitis: The Pathogenesis Revisited
.Ocul Immunol Inflamm. 2004 Dec;12(4):255-85.

Quentin Sattentau
Avoiding the void: cell-to-cell spread of human viruses
Nature Reviews Microbiology 6,  (November 2008). 815-826. 

Herpes simplex virus resistance to antiviral drugs.
Journal of Clinical Virology. (2003). 29-37.

1 comment:

  1. Most people get HSV-1 (herpes simplex type 1) as an infant or child. This virus can be spread by skin-to-skin contact with an adult who carries the virus. An adult does not have to have sores to spread the virus.
    Herpes Simplex