March 09, 2007
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Rockefeller University scientists researching the HIV virus recently discovered how a protein commonly found in the liver is necessary for Hepatitis C infection. By targeting this specific protein, scientists may develop more effective treatment strategies for Hepatitis C.
http://newswire.rockefeller.edu
February 26, 2007
Key protein for hepatitis C virus entry identified
For as many as 200 million people worldwide infected with hepatitis C, a leading cause of chronic liver disease, treatment options are only partially effective. But new research by Rockefeller University scientists points to a potential new target for better drugs: a key protein that resides in human liver cells that hepatitis C requires for entry.
Scientists have known that for HCV to infect human cells, at least two molecules — CD81 and SR-B1 — must be present on the surface of the cell. However, they suspected that at least one other molecule also has to be present, because in some cells that contained the known molecules HCV was still unable to gain entry.
Co-first authors Matthew Evans and Thomas von Hahn, postdoctoral associates in Rockefeller’s Laboratory of Virology and Infectious Disease led by Charlie Rice, set out to find the missing receptor. HCV is notorious for being too difficult to replicate in cell culture, so Evans and von Hahn used HCV “pseudoparticles,” HIV particles in which the HIV envelope proteins are replaced with those from HCV. This replacement tricks the host cell into allowing the engineered particle to enter in a manner identical to that of authentic HCV. Once inside the cell, however, the HIV replication machinery takes over.
In order to identify potential entry receptors, Evans and von Hahn teamed up with co-authors Theodora Hatziioannou and Paul Bieniasz, HIV researchers at Rockefeller and the Aaron Diamond AIDS Research Center who had developed a special multiple-round screening technique. The screen pointed them to claudin-1, a protein involved in the maintenance of cell structures called tight junctions that is found in several epithelial tissues in the body, and is most prevalent in the liver.
A series of experiments on various human cell lines confirmed that claudin-1 is a requirement for HCV entry, says von Hahn. The research showed that the HCV pseudoparticle was able to enter cells that contain claudin-1, as well as claudin-1-deficient cells that were made to artificially express the protein, but not other cells. “We did not see HCV enter any cell that did not have claudin-1,” says von Hahn.
Further experiments showed that claudin-1 only appears to come into play after the virus has bound to the cell, perhaps as a means for the virion to actually be taken up by the cell or facilitate fusion between the virus and cell membranes. The scientists reported their findings this week in an advance online publication in the journal Nature.
The researchers believe that there may be additional receptors – yet to be identified – that are necessary for HCV to infect cells, as some human cell lines contain all three receptors but still do not become infected. HCV also does not enter some human cells that express all three factors, nor can it infect mouse cells that have been engineered to express the three human receptors.
The identification of claudin-1, and the possible discovery of additional host cell receptors, offers the promise of new avenues for anti-HCV therapeutics, according to the authors.
“Anti-HCV drugs currently under development are directed against viral enzymes required for viral replication, to which the virus can readily evolve resistance,” says Evans. “HCV may be less able to develop resistance to drugs targeting receptors on the host cell.”
“We also foresee the potential for combination therapies, which would attack different stages of HCV infection, much like the HIV cocktail that has been so effective,” says Rice, who is the Maurice R. and Corinne P. Greenberg Professor and scientific director of the Center for the Study of Hepatitis C, a cooperative endeavor of Rockefeller, Weill Medical College of Cornell University and NewYork-Presbyterian Hospital.
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March 08, 2007
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With over 5 million Americans infected, the Hepatitis C virus is the most common cause of liver disease today. Although it is believed to be primarily transmitted through blood to blood contact, there are indications that other means of contracting Hepatitis C are possible. Of primary interest to those concerned with the number one cause of liver disease is the possibility of transmitting Hepatitis C via saliva.
by Nicole Cutler, L.Ac.
As the most common chronic blood borne infection in the United States, the concentration of Hepatitis C virus in a drop of infected blood is exponentially higher than the concentration of HIV in a drop of infected blood. This explains why it is important to avoid anything that could possibly be tainted with any amount of blood. While not normally found in urine, semen, vaginal/cervical fluids, feces or saliva, injury or illness may cause some of these substances to be contaminated with blood.
In nearly half the cases of Hepatitis C, the infected individuals cannot identify the source for their infection. While it is believed most cases are due to risk factors involving contaminated blood, there remain unidentified modes of Hepatitis C transmission. Salivary transmission is one potential explanation for many unexplained viral causes.
Tiny and Infectious
Measuring only about 50 nanometers in diameter, Hepatitis C is an extremely small virus. A nanometer is one billionth of a meter; 200,000 Hepatitis C viruses placed end to end would only measure a single centimeter. Smaller than the wavelength of visible light, viral particles have no color. In those who are infected, Hepatitis C may produce approximately one trillion new viral particles every day.
Unlike many other viruses (like HIV), any potential source of blood to blood contact seems capable of carrying the Hepatitis C virus. This is true, even if the source is indirect, such as a used razor, making HCV far more transmissible than most other blood borne viruses. As documented by occupational exposure statistics, Hepatitis C is approximately seven times more infectious than HIV.
Saliva
People with chronic Hepatitis C are advised not to share toothbrushes, razors, nail clippers or other personal articles that may have potentially been in contact with their blood. While there is very little emphasis on saliva as a vehicle of Hepatitis C transmission, under the right circumstances there is some evidence to the contrary:
1. As published in the September 2006 issue of Journal of Viral Hepatitis, German researchers investigated the transmission of Hepatitis C via a toothbrush. A team from the University of Regensburg examined 30 patients with Hepatitis C to see whether they had contaminated their toothbrushes with the virus. They collected saliva samples from infected patients both before and after tooth brushing. Figures showed that 30 percent of infected patients tested positive for traces of the virus in their saliva before brushing their teeth, while 38 percent tested positive in their saliva after brushing. Additionally, about 40 percent of the water used to rinse the infected toothbrushes tested positive for the virus. This information confirms the caution against toothbrush sharing, and also sounds a possible Hepatitis C transitory alarm.
2. In September of 2003, evidence that saliva contains the Hepatitis C virus was disclosed at the Interscience Conference on Antimicrobial Agents and Chemotherapy. Scientists from the University of Washington in Seattle concluded that while saliva may be infectious, the strongest predictor of viral presence in the saliva is serum viral load. Researchers found that Hepatitis C was not found in saliva if the person’s viral load was under one million. Additionally, any risk of acquiring infection through salivary contact existed only in the presence of gum disease. Investigators attribute this risk to microscopic amounts of blood in the saliva and visually undetectable open mouth wounds present in gum disease.
All possibilities must be considered in trying to determine how unknown sources of Hepatitis C infection took place. Although Hepatitis C has been detected in saliva, the necessary conditions render it unlikey—but not impossible—to be transmitted by kissing or through the sharing of a toothbrush. Before anybody panics about these potential risks, remember that there are conditions accompanying these possible modes of transmission:
· The person with the virus must have a viral load over one million.
· Both parties involved have gum disease.
While experts view the risk of transmitting this disease through saliva as extremely low, it is recommended to maintain good oral hygiene, and toothbrushes be used solely by their owners.
References:
Jancin, Bruce, Hepatitis C virus may be spread through saliva: avoid toothbrush sharing, OB/GYN News, November 2003.
Hepatitis C – contamination of toothbrushes: myth or reality?, Journal of Viral Hepatitis, September 2006.
www.cdc.gov, Hepatitis C FAQ, US Department of Health and Human Services, 2006.
www.epidemic.org, The Hepatitis C Virus, Trustees of Dartmouth College, 2006.
www.hcvadvocate.org, HCV: Important Study on Dried Blood Stability, Hepatitis C Support Project, January 2004.
www.hcvets.com, Saliva may have infectious amounts of HCV in presence of high HCV viral load and gum disease, Michael Carter, HCVets.com, September 2003.
www.hepnet.com, Stopping the Spread of the Virus, Molly Colin, Schering Canada Inc., 2006.
www.medicalnewstoday, Kissing Could Spread Hepatitis C, MediLexicon International, Ltd., September 2003.
www.pafp.com, Hepatitis C Virus can Live in Dried Blood, Pennsylvania Academy of Family Physicians, 2003.
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