August 24, 2011

New Protein Could Be Key Tool For Stopping Ebola Outbreaks


Researchers at Albert Einstein College of Medicine of Yeshiva University have identified a cellular protein used by the deadly Ebola virus.

The findings suggest a possible strategy for blocking infection caused by the Ebola virus, which is one of the world's most lethal viruses.

The virus is notorious for killing up to 90 percent of the people it infects.  It first emerged in 1976 in villages along the Ebola River in the Sudan and the Democratic Republic of Congo, Africa.

The Ebola virus binds to the host cell's outer membrane, and a portion of host cell membrane then surrounds the virus and pinches off, creating an endosome.  Endosomes carry viruses deep within the cell and eventually mature into lysosomes, which are tiny enzyme-filled structures that digest and recycle cellular debris.

The researchers looked for proteins that Ebola virus might exploit to enter the cell's cytoplasm.  The protein Niemann-Pick C1 (NPC1) stood out to the team.

"We found that if your cells don't make this protein, they cannot be infected by Ebola virus," Kartik Chandran, assistant professor of microbiology & immunology at Einstein, said in a press release. "Obviously it's very early days, but we think our discovery has created a real therapeutic opportunity."

The protein is embedded with cell membranes, where it helps transport cholesterol within the cell.

The absence of NPC1 due to gene mutations causes a rare degenerative disorder known as Niemann-Pick disease.

The researchers analyzed mice carrying a mutation in NPC1 with Ebola virus to confirm their finding that the protein is crucial for Ebola virus infection.

The researchers also tested whether other major viruses need NCP1 to infect human cells.  Only Ebola virus and its close relative, Marburg virus, were found to be equipped with the NPC1 protein for infection.

"Our work suggests that these viruses need NPC1, which is embedded in the lysosomal membrane, to escape from the lysosome into the cytoplasm," Chandran said in a press release. "We are now testing that hypothesis in the laboratory."

The new discovery could play a crucial role in Ebola outbreaks by helping to create a drug that blocks the action of NPC1.

"Even though such a treatment would also block the cholesterol transport pathway, we think it would be tolerable," said Dr. Chandran. "Most outbreaks are short-lived, so treatment would be needed for only a short time."

The findings were published in Wednesday's online edition of the journal Nature.


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