Navigation Links
Achilles heel of the herpes virus possibly found

It's one of the most common viruses in America, and one that causes the most guilt and shame. It can get inside almost any kind of human cell, reproduce in vast numbers, and linger for years in the body, causing everything from recurrent genital blisters to sores around the mouth. Its complications can kill, and it may increase susceptibility to many nerve and brain disorders.

But until now, scientists haven't fully understood how the herpes simplex virus (HSV) manages to do all of this. And that has stood in the way of developing more targeted, effective treatments against it to help those infected.

New research from the University of Michigan Medical School may help change that.

An estimated 45 million Americans have genital herpes and millions more have the more visible oral variety. Once someone is infected, they're infected for a lifetime. New medicines for herpes infection are badly needed; currently, antiviral drugs can quell symptoms of an outbreak, but not eliminate the virus. And, there's increasing evidence that HSV may damage the nerve cells in which it hides between outbreaks, possibly contributing to neurological disease.

In a presentation Sunday at the International Congress of Virology and in two new papers in the Journal of Virology, U-M researchers are reporting the discovery of a receptor that appears to function as one "lock" that HSV opens to allow it to enter human cells. They've also found the gene that controls the production of that receptor, deciphered some aspects of the receptor's structure, and developed a pig-cell system that could be used to test new anti-herpes drugs.

The findings may help explain why the oral and genital herpes virus has such a successful track record: The receptor, dubbed B5, is made by most cells for another purpose not yet understood. HSV appears to have evolved a way to latch onto it, and fool the cell into letting the virus in. And since most cells express the gene for the B5 receptor, this may be a reason HSV can get into most kinds of cells.

"This may be one central part of the Achilles' heel in interactions of herpes virus with a cell to start infection. We can use the receptor molecule to try to understand the process and perhaps combat infection at this vulnerable site," says A. Oveta Fuller, Ph.D. the leader of the U-M team, senior author on the two papers and an associate professor in the U-M Medical School's Microbiology and Immunology Department. "While we're still a few years away from being able to use this new knowledge to find effective drug candidates, this is a very exciting confluence of discoveries."

The U-M holds a patent on the system and methods that the team used to make the discoveries.

Coincidentally, the U-M team's findings about the B5 receptor are being published at about the same time as an Italian team's reports about a possible 'key' on the herpes simplex virus surface that may match the 'lock' found by the U-M team. The Italian team has identified a region of a viral surface protein that matches the U-M team's predictions of what the virus likely would use to bind and engage the B5 receptor.

"It appears that B5 is a new class of viral receptor. Unlike other viruses so far, HSV seems to have evolved to take advantage of a broadly present cellular protein that has properties like that of known cellular fusion machinery," says Fuller. "No other virus has been shown to use a cellular fusion protein for entry into cells."

She explains that the search for the mechanisms by which HSV enters cells has been hindered by the fact that the virus is very good at entering so many kinds of cells. The many possibilities for virus binding to cells make deciphering the entry process a difficult problem to solve.

The gene that encodes B5 had in fact been sequenced, but not characterized, as part of the Human Genome Project. Discovering its role and studying the HSV entry mecha nism was tricky and near impossible until Fuller's team discovered a type of pig kidney cell that isn't vulnerable to infection by human herpes virus. They searched the genome library to find genes essential to HSV infection, isolated the B5-coding sequence, and figured out how to get pig cells to express the human B5 protein to allow the pig cells to be infected with human herpes virus.

For these studies, Fuller credits the persistence of research team members in working with the genomic library and culture of human and pig cells, especially U-M doctorate graduate Aleida Perez and postdoctoral fellows Qingxue Li and Pilar Perez-Romero. Perez-Romero is first author of one of the two new papers, and a co-author on the other.

The two new papers show that the B5 receptor has important features that could explain why it is important to HSV's ability to fuse with the fluid membrane that encloses every human cell. The researchers were able to show that by placing only the DNA sequence that encodes B5 into HSV-resistant pig cells, they could make the pig cells susceptible to HSV. They were also able to block viral infection of both human cells and susceptible pig cells by adding to cell cultures a synthetic peptide made to mimic the structure of a smaller region of the B5 receptor. This peptide looks like a functional region of B5 and apparently interferes with virus engaging of the cell receptor.

The papers detail how the team isolated and characterized the gene that encodes B5, called hfl-B5, and used the DNA sequence to find out more about the protein structure of the B5 receptor. In the presentation at the International Congress for Virology, Fuller will describe recent findings that further confirm B5's importance in HSV infection.

The virology team reports that the B5 molecule appears to form a shape called a coiled coil. This intricately wound structure, they believe, may be similar to the structure of some fusion proteins of viruses and also to cellular proteins called SNAREs. Typically, SNARE proteins help cells to manage the fusion of membranes of vesicles inside the cell with other specific vesicles. Vesicles are tiny membrane-encased packets that encapsulate neurotransmitters, enzymes or other important substances and allow them to be transported within and between cells.

The researchers were able to show that B5 sits in the cell membrane with one end of the protein exposed outside of the cell ready to link up with viruses -- or to serve the receptor's "real" function, which still remains to be discovered. They also showed that HSV does not enter into pig cells that have an altered human B5 protein that is changed by mutations that affect a functional region important to forming a coiled coil.

"If B5 is a SNARE-like cell fusion receptor", Fuller says, "it may turn out to be useful for more than HSV drug treatment. It could act as a way to link vesicles containing drugs with cells, and deliver them inside". She is currently collaborating with U-M nanotechnology researchers on this concept.

The findings suggest that B5 or its viral ligand could be a target for antiviral treatment, much like cell receptors for the entry of human immunodeficiency virus (HIV) into cells have become targets for new AIDS drugs.


'"/>

Source:University of Michigan Health System


Related biology news :

1. Researchers develop new method to help find deadly malaria parasites Achilles heel
2. Association of herpesvirus with lung disorder questioned
3. Topical treatment shown to inhibit HIV and herpes simplex virus infection
4. Live vaccines more effective against horse herpes virus
5. Landmark discovery of a Kaposis sarcoma-associated herpesvirus receptor
6. Knowledge of infection may prevent spread of herpes virus
7. Study shows how herpes infects cornea, evades immune cells
8. Research holds promise for herpes vaccine
9. UCSF study will test new vaginal microbicide for herpes and HIV
10. Anti-herpes treatment reduces HIV levels in women infected with both viruses
11. Insulator helps silence genes in dormant herpes virus
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/7/2017)... 2017   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that the latest ... highly flexible and award winning eClinical solution, is now ... is a proven Software-as-a-Service (SaaS) clinical research technology ... but also delivers an entire suite of eClinical tools ...
(Date:2/7/2017)... 2017 Ipsidy Inc. ( www.ipsidy.com ... IDGS], ("Ipsidy" or the "Company") a provider of secure, ... is pleased to announce the following changes as part ... January 31, 2017, Philip D. Beck was ... President.  An experienced payment industry professional and public company ...
(Date:2/3/2017)... , Feb. 3, 2017  Texas Biomedical Research Institute ... Larry Schlesinger as the Institute,s new President ... Biomed effective May 31, 2017. He is currently the Chair ... of the Center for Microbial Interface Biology at Ohio State ... as the new President and CEO of Texas Biomed," said ...
Breaking Biology News(10 mins):
(Date:2/15/2017)...  Trianni, Inc. („TRIANNI") gab heute bekannt, man ... über die Verwendung der The Trianni Mouse unterschrieben, ... Entdeckung monoklonaler Antikörper. Die Trianni Plattform ... das Janssen den Zugang zu einer ... für die schelle Isolierung vollständig menschlicher Therapeutika optimiert ...
(Date:2/15/2017)... 2017  Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA), ... fourth quarter and full year ended December 31, ... for Vanda as we continued to demonstrate strong ... exclusivity for Fanapt," said Mihael H. Polymeropoulos, M.D., ... pipeline with important 2017 milestones underscores Vanda,s commitment ...
(Date:2/15/2017)... Feb. 15, 2017 Windtree Therapeutics, Inc. (Nasdaq: ... developing aerosolized KL4 surfactant therapies for respiratory diseases, will ... presentation) at 8:00 AM EST on Thursday, February 16, ... clinical program, the recently announced closing of a $10.5 ... To participate in the live call and ...
(Date:2/15/2017)... ... February 15, 2017 , ... Diameter Health ... Diameter Health technology in the hands of Lantana analysts. The high-performance platform of ... and public health entities – all those mining value from clinical data – ...
Breaking Biology Technology: