WASHINGTON, May 27 (PNA/Xinhua) — Researchers from the United States and the Netherlands said Tuesday they have identified Ebola’s Achilles’ heel that could be targeted to completely block the deadly virus’s infection.
The researchers reported in the online U.S. journal mBio that Ebola can’t infect mice unless it first attaches to a host protein called Niemann-Pick C1 (NPC1).
“Our study reveals NPC1 to be an Achilles’ heel for Ebola virus infection,” co-study leader Kartik Chandran, associate professor of the Albert Einstein College of Medicine of Yeshiva University, said in a statement.
“Mice lacking both copies of the NPC1 gene, and therefore devoid of the NPC1 protein, were completely resistant to infection. ”
Previous in vitro studies have demonstrated that Ebola enters host cells by binding directly to NPC1, and that blocking the ability of the virus to engage NPC1 prevents Ebola infection.
To test whether this was also true in vivo, the team exposed three types of mice to Ebola: wild-type or normal mice, “knockout mice” that were genetically engineered to be completely deficient in NPC1, and “carrier mice” engineered to have both a normal and a mutant NPC1 allele.
While the wild type mice succumbed to the infection, the “knockout mice” were entirely free of virus replication and completely protected against the disease, they found.
“Carrier mice” initially had high levels of Ebola viremia, but the levels quickly decreased as the host immune response effectively cleared the virus.
“The underlying story of an Ebola infection is that your immune system and the virus are in a race,” said co-study leader John Dye, branch chief of viral immunology at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).
“If you can do anything to control the amount of virus that is in the system, keep it below a certain threshold, your immune system in many cases will win that race.”
NPC1 helps transport cholesterol within the cell. People lacking NPC1 due to genetic mutations develop a fatal neurodegenerative disorder called Niemann-Pick disease, which is sometimes referred to as childhood type of Alzheimer’s disease.
Even though such a treatment in humans would also block the cholesterol transport pathway, “we think patients would be able to tolerate the treatment, which would be needed for only a short time,” said Andrew Herbert, senior research scientist in the viral immunology branch at the USAMRIID, and co-first author of the study.
The team hoped that future research in humans could lead to the development of antiviral drugs that can effectively target NPC1 and prevent infection by Ebola and other highly virulent filoviruses, which also require NPC1 as a receptor.
Currently, there are no approved treatments for Ebola, and all of the therapies in the drug pipeline focus on attacking the virus. Targeting NPC1 is the first host-based therapeutic approach. (PNA/Xinhua)