Navigation Links
Inheriting a tendency to brain infection

Might some infectious diseases run in families because one inherits susceptibility to them? Although researchers generally agree that an individual's genetic makeup contributes in subtle ways to susceptibility to infectious disease, new findings from researchers in France support the controversial idea that an error in a single gene is enough to dramatically alter an individual's susceptibility to certain infections.

Howard Hughes Medical Institute (HHMI) international research scholar Jean-Laurent Casanova and Emmanuelle Jouanguy of the Necker Medical School in Paris, along with other colleagues have identified a single gene that predisposes individuals to herpes simplex encephalitis, an infectious disease that tends to be extremely choosy about its victims. In a paper published in the September 29, 2006 issue of the journal Science, they describe two young patients who carry mutations in this gene who are susceptible to the disease while being otherwise immunologically normal. The paper was published in advance online.

As many as eight out of 10 adults are infected by the herpes simplex virus. For most, the worst symptom is a cold sore, but in some individuals, the virus causes inflammation of the brain that can lead to mental retardation, epilepsy, or death. Until now, scientists have been unable to identify any specific risk factors for the disease.

Five years ago, Casanova began to suspect that those who were susceptible to the inflammatory brain disease were in fact genetically predisposed to it. There was little published evidence that herpes simplex encephalitis ran in families, which suggested to him that if a genetic element was at work, it was probably recessive: an individual had to carry two copies of the affected gene to show the predisposition.

Evidence he collected during an epidemiological survey in France supported that idea. The survey, conducted with pediatric neurologist Marc Tardieu of the Kremlin-BicĂȘtre hospital in Paris and genetic epidemiologist Laurent Abel of the Necker Medical School, revealed that a significant proportion of patients with herpes simplex encephalitis had parents who were blood relatives --often first or second cousins--and were therefore at higher than normal risk of inheriting two copies of a faulty gene.

In 2005, Casanova later identified a 15-year-old boy who developed brain damage due to herpes simplex infection. Casanova found that the boy's blood cells failed to produce an important immune signalling molecule, type I interferon, when challenged with the virus in a laboratory flask.

At about the same time, Bruce Beutler of the Scripps Research Institute in La Jolla, California created a mutant mouse that did not respond to certain molecules that normally trigger cells to produce type I interferon. The mouse turned out to be vulnerable to a range of infections, but its susceptibility to herpes simplex had not been tested. "Nevertheless," said Casanova, "the immunological abnormality perfectly matched that found in our patient."

Beutler's mouse carried a mutation in a gene called unc93b. The French team sequenced the human counterpart, unc93b1, and found that their patient carried two mutated copies of this gene. In early 2006, they found a second, unrelated patient who had also inherited two mutated copies of the gene--although the mutation in her case was different. She had survived two episodes of the disease, which had left her partially paralysed and mildly mentally retarded.

The link between interferon production and the disease suggests a new strategy for treatment, Casanova said. "It's like giving insulin to a diabetic patient," he said. "You just replace the missing compound."

Soon, children who come into the intensive care unit with herpes simplex encephalitis may be treated with both the standard antiviral, acyclovir, and with type I interferon, to replace the interferon they lack if they have the mutation, said Casanova. That hasn't happened yet, although patients susceptible to tuberculosis (TB) because of an inherited deficiency in another interferon pathway have been successfully treated with the interferon they lack. Based on the results in patients with TB, Casanova hopes the combined treatment could dramatically accelerate recovery from herpes simplex encephalitis, and thereby also limit potential brain damage.

Casanova believes there are likely other genes that predispose people to infectious diseases, and that some of them may be inherited in a dominant fashion. That is, an individual need inherit only one copy of the mutation to show the predisposition. In his opinion, scientists will increasingly need to view common infectious diseases through the lens of such primary immunodeficiencies.

"Understanding the genetic basis of the failure of the immune system should make it possible to devise novel ways to make it succeed," he said.

Since the mid-1950s, most infectious disease researchers have believed that the genetic components of infectious disease are complex, involving different genetic variants interacting with each other and with the environment in subtle ways that add up to an overall predisposition or resistance.

However, Michael Levin, professor of pediatrics and international child health at Imperial College, London, does not think the two theories are mutually exclusive. "We strongly suspect that rare, highly deleterious mutations may co-exist with common polymorphisms in many infectious diseases," he said.
'"/>

Source:Howard Hughes Medical Institute


Related biology news :

1. A link is found between morphine addiction and the tendency to explore
2. Controversial drug shown to act on brain protein to cut alcohol use
3. Mouse brain cells rapidly recover after Alzheimers plaques are cleared
4. Mouse brain tumors mimic those in human genetic disorder
5. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
6. First atlas of key brain genes could speed research on cancer, neurological diseases
7. NYU study reveals how brains immune system fights viral encephalitis
8. Stem cells from brain transformed to produce insulin at Stanford
9. Birds brains reveal source of songs
10. Loves all in the brain: fMRI study shows strong, lateralized reward, not sex, drive
11. Revolutionary nanotechnology illuminates brain cells at work

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/3/2016)... February 3, 2016 --> ... research report "Automated Fingerprint Identification System Market by Component ... Application (Banking & Finance, Government, Healthcare, and Transportation) and ... the market is expected to be worth USD 8.49 ... between 2015 and 2020. The transformation and technology evolution ...
(Date:2/3/2016)... 2016 http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ... "Emotion Detection and Recognition Market by ... Software Tools (Facial Expression, Voice Recognition and ... - Global forecast to 2020" report ... http://www.researchandmarkets.com/research/d8zjcd/emotion_detection ) has announced the addition of ...
(Date:2/2/2016)... YORK , Feb. 2, 2016 ... of the bioinformatic market by reviewing the recent ... enabled tools that drive the field forward. Includes ... to: Identify the challenges and opportunities that ... providers and software solution developers, as well as ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... Feb. 11, 2016  Dovetail Genomics™ LLC today announced ... program for a planned metagenomic genome assembly service. ... metagenomic genome assembly method in a talk on Friday, ... & Technology conference in Orlando, Fla. ... complex datasets is difficult. Using its proprietary ...
(Date:2/11/2016)... ... 2016 , ... Global Stem Cells Group, has ... The new facility will provide advanced protocols and state-of-the-art techniques in cellular medicine, ... , The new GSCG clinic is headed by four prominent Ecuadorian physicians, including ...
(Date:2/10/2016)... , Feb.10, 2016 ASAE is introducing a ... Management Companies (AMC) the option of joining or renewing ... fee determined by staff size, every employee in any ... ASAE and reap all available member benefits.   ... new organizational membership options will allow organizations of any ...
(Date:2/10/2016)... ... February 10, 2016 , ... Benchmark Research, a fully-integrated network ... two long-standing principal investigators (PI) to the roles of Chief Medical Officer, Clinical ... Dr. Laurence Chu, a Benchmark Research PI in the Austin office, will assume ...
Breaking Biology Technology: