Archive for the ‘ebola’ Category

by Jennifer Brown

The recent Ebola outbreak in West Africa has claimed more than 11,300 lives—a stark reminder of the lack of effective options for treating or preventing the disease.

Progress has been made on developing vaccines, but there is still a need for antiviral therapies to protect health care workers and local populations in the event of future outbreaks.

Now, a new study suggests that gamma interferon, an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus.

The findings, published in the journal PLOS Pathogens, show that gamma interferon, given up to 24 hours after exposure, inhibits Ebola infection in mice and completely protects the animals from death.

Ebola infection appears to be a stepwise process. First, the virus targets and infects macrophages or dendritic cells, two types of immune system cells found in the liver, spleen, and lymph nodes. Ebola then replicates in those cells. Following this initial infection, which happens at day 3 or 4 in non-human primates, Ebola virus is released into the blood and infects a plethora of other different cell populations.

“It goes from an early stage with a very targeted infection of only these few cell types, to everything being infected,” says Wendy Maury, professor of microbiology at the University of Iowa.

“We think what’s happening with gamma interferon is that it’s targeting macrophages and blocking the infection of those initial cell targets so you don’t get the second round of infection.”

The University of Iowa does not have a specializing BioSafety Level 4 (BSL4) lab that is required for experiment using Ebola virus, so the researchers made their initial findings using a surrogate virus, which targets and infects the same cells as Ebola, but does not cause the disease.

This Ebola lookalike—a sheep in wolf’s clothing—consists of a less dangerous vesicular stomatitis virus (VSV) that expresses Ebola glycoproteins on its surface.

All of the results found using the surrogate virus were then repeated using mouse-adapted Ebola virus in the BSL4 lab of Maury’s longtime collaborator Robert Davey at Texas Biomedical Institute in San Antonio, Texas.

Gamma interferon inhibits the virus’s ability to infect human and mouse macrophages, in part by blocking virus replication in the cells. Pre-treating mice with interferon gamma 24 hours before exposure protects the animals from infection and death. The researchers were surprised to find that treatment up to 24 hours after what would have been a lethal exposure also completely protected the animals from death, and they could no longer detect any Ebola virus in the mouse’s cells.

The findings suggest that interferon gamma may be useful both as a prophylaxis and post-exposure treatment against Ebola. The team still has to determine how late gamma interferon can be given to the mice and still prevent infection. However, the results suggest a window of time after exposure when gamma interferon may be an effective antiviral therapy.

“My guess is that if you delay the gamma interferon too much, you miss this window of opportunity to block the infection in macrophage cells and the gamma interferon can no longer provide protection,” Maury says.

Maury and colleagues investigated how gamma interferon might be helping the cells fight off the Ebola virus. They identified that the expression of more than 160 genes in human macrophages is stimulated by gamma interferon. Introduction of some of these genes into cells was sufficient to prevent Ebola infection.

“This mechanistic information might suggest more precise drug targets rather than the broad effects, including adverse side-effects, that are produced by gamma-interferon,” she says.

Gamma interferon is already approved by the FDA to treat chronic granulomatous disease (an immune disease) and severe malignant osteopetrosis.

In addition to moving the studies into larger animal models, Maury next plans to study the ability of gamma interferon to inhibit Ebola infection in conjunction with other developing antivirals.

“Right now, there are no FDA-approved antiviral therapies for Ebola, but there are some being developed that target virus entry,” she says. “We know that gamma interferon blocks replication but not entry into cells. So combining an entry inhibitor with gamma interferon may allow us to reduce amount of gamma interferon needed and target two different steps in the virus’s life cycle, which has been shown in HIV to be critically important for controlling the virus.”

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005263

http://now.uiowa.edu/2015/12/fda-approved-drug-protects-mice-ebola

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American doctor Ian Crozier was treated for Ebola in Atlanta last year and declared free of the virus in his blood. But he had no way of knowing it still lurked in his eye.

About two months after being released from the hospital, he experienced a piercing pain in his left eye, he told The New York Times. The pressure in his eye elevated while his vision decreased.

After repeated tests, doctors discovered the virus was still living in his eye.

“It felt almost personal that the virus could be in my eye without me knowing it,” he told the paper.

His case has left doctors stunned and highlighted the need for eye checkups for Ebola survivors.

Crozier, 44, was hospitalized at Emory University Hospital for more than a month in September after contracting the disease in Sierra Leone, where he worked at a hospital.

At the time, the hospital said he was the sickest of all the four Ebola patients treated there.

Crozier was discharged in October, and about two months later, he developed eye problems and returned to Emory. Doctors stuck a needle in his eye and removed some fluid, which tested positive for the virus.

“Following recovery from Ebola virus disease, patients should be followed for the development of eye symptoms including pain, redness, light sensitivity and blurred vision, which may be signs of uveitis,” said Steven Yeh, associate professor of ophthalmology at Emory University School of Medicine.

Uveitis is an inflammation of the eye’s middle layer. Ebola is also known to live in semen months after it’s gone from the blood.

No risk of spreading the virus

Despite the presence of the virus in the eye, samples from tears and the outer eye membrane tested negative, which means the patient was not at risk of spreading the disease during casual contact, Emory said in a statement Thursday.

It did not name the patient, but The New York Times did. The New England Journal of Medicine also released a study on the case.

Though the patient was not at risk of spreading the virus, all health care providers treating survivors, including eye doctors, must follow Ebola safety protocols, said Jay Varkey, assistant professor at Emory University School of Medicine.

Ebola patient for a second time

When the virus was found in Crozier’s eye, the eye started losing its original blue hue, he told the paper.

Bewildered, doctors tried different forms of treatment as he relived his Ebola nightmare.

They gave him a steroid shot above his eyeball and had him take an experimental antiviral pill that required special approval from the Food and Drug Administration, the Times reported.

His eye gradually returned to normal, but it’s unclear whether it was as a result of the steroid shot, pill or his body’s immune system.

While Ebola survivors in West Africa have reported eye problems, it’s unclear how prevalent the condition is and how often it happens.

“These findings have implications for the thousands of Ebola virus disease survivors in West Africa and also for health care providers who have been evacuated to their home countries for ongoing care,” Varkey said. “Surveillance for the development of eye disease in the post-Ebola period is needed.”

http://www.cnn.com/2015/05/08/health/ebola-eye-american-doctor/index.html

A family of viruses that Ebola belongs to may have existed over 20 million years ago, according to a new study published in the journal PeerJ.

Researchers from the University of Buffalo found that Filoviruses did not begin appearing 10,000 years ago as previously thought, but in fact have been around for much longer. The Ebola virus belongs to the family of filoviruses, also known as the Filoviridae family. “Filoviruses are far more ancient than previously thought,” said Derek Taylor, lead author of the study and a professor of biological sciences at the University of Buffalo, in the press release. “These things have been interacting with mammals for a long time, several million years.”

Despite the fact that scientists around the world are frantically searching for a cure and better treatment for Ebola, there’s still much to learn about the deadly virus. The authors of the study argue that better understanding Ebola’s evolutionary roots could “affect design of vaccines and programs that identify emerging pathogens.”

The study focused not on Ebola specifically, but the ancestors and family of Ebola to better understand where it may have come from. Both the Ebola virus and Marburg virus — also a hemorrhagic fever virus that belongs to the Filoviridae family — were found to be tied to ancient evolutionary lines, and they shared a common ancestor 16 to 23 million years ago. The authors discovered this by examining viral fossil genes, which are bits of genetic material that animals acquire from viruses during infection. They found Filovirus-like genes in rodents, particularly hamsters and voles, which means that the filovirus family is likely as old as these rodents’ common ancestor. The genetic material in these fossils were more closely related to Ebola than Marburg, meaning the two lines had already begun to diverge during the Miocene Epoch, a time period that occurred five to 23 million years ago. During this time, there were also warmer climates, as well as the first appearances of kelp forests and grasslands on Earth.

“These rodents have billions of base pairs in their genomes, so the odds of a viral gene inserting itself at the same position in different species at different times are very small,” Taylor said. “It’s likely that the insertion was present in the common ancestor of these rodents.”

The Filoviridae family is defined by viruses that form virions, or filamentous infectious viral particles. The Ebola virus and Marburg virus are the most well-known among this group, and they are both severe viruses that cause hemorrhagic fevers in both animals and humans (essentially, they’re deadly diseases that lead to fever and bleeding).

Taylor believes that the study may help in the fight against Ebola by widening our knowledge about its history, and identifying what species are most likely to be hosts of the virus. “When they first started looking for reservoirs for Ebola, they were crashing through the rainforest, looking at everything — mammals, insects, other organisms,” Taylor said. “The more we know about the evolution of filovirus-host interactions, the more we can learn about who the players might be in the system.”

Source: Taylor D, Ballinger M, Zhan J, Hanzly L, Bruenn J. Evidence that ebolaviruses and cuevaviruses have been diverging from marburgviruses since the Miocene. PeerJ. 2014.

http://www.medicaldaily.com/ebolas-family-tree-disease-may-have-existed-23-million-years-much-longer-previously-307958