Tag: Ebola

Retinal Cells a Haven for Ebola and Other Viruses

Credit: National Eye Institute

A specific cell within the retina, the retinal pigment epithelial cell, appears to be particularly good at housing Ebola and other viruses, according to new research published in the journal Frontiers in Virology.

“Inflammation of the eye, known as uveitis, is very common following infection with Ebola and we know the cells within the iris, at the front of the eye, as well as the retina have the capacity to play a major role in uveitis and act as hosts for microorganisms,” explained study senior author Professor Justine Smith at Flinders University.

“However, what we didn’t know was which out of the two was most responsible in the case of Ebola.”

“Patients with Ebola eye disease have characteristic retinal scars”

Professor Justine Smith

The study used cells from human eyes donated from the South Australia Eye Bank to investigate the ability of iris and retinal pigment epithelial cells to be infected by Ebola.

Cells were infected with Ebola virus, Reston virus (a type of ebolavirus that does not cause disease in humans) or Zika virus (another type of virus, but one that also can cause uveitis), while some were left uninfected for the duration of the trial.

While both types of cells allow replication of the Ebola virus, it was the retinal cells that showed much higher levels of infection.

“We also found similar results when looking at the cells infected with Reston virus and Zika virus,” said Professor Smith.

“Patients with Ebola eye disease have characteristic retinal scars, suggesting the retinal pigment epithelium is involved in the disease, so this finding is consistent with what eye doctors are seeing in the clinic.

“These retinal cells are good at eating things – called phagocytosis – and they play an essential part in the visual cycle by recycling our photoreceptors, so it makes sense that these cells would be a receptive haven for Ebola, as well as other viruses.”

The researchers say the study demonstrates an important target cell for Ebola infection in the eye and suggests the potential for these cells to be monitored during acute viral infection to identify patients at highest risk of uveitis.

“Amongst other issues, including pain and blurred vision, uveitis can ultimately lead to vision loss, so it’s important we find ways to diagnose it as early as possible to enable swift treatment,” said Professor Smith.

Source: Flinders University

The Ebola Relative, Lloviu Virus, Has Pandemic Potential

Photo by Todd Cravens on Unsplash

Researchers have helped isolate the Lloviu virus (LLOV), a close relative of Ebola virus, for the first time, showing that it could cross over into humans, highlighting the need for future research to ensure pandemic preparedness. The study is reported in Nature Communications.

LLOV is part of the filovirus family, which also includes the Ebola virus. While Ebola (and other filoviruses including the lethal Marburg virus) have only occurred naturally in Africa, Lloviu has been discovered in Europe. The filovirus LLOV, was genetically identified in 2002 in Schreiber’s bats in Spain and was subsequently detected in bats in Hungary.

As a zoonotic virus, LLOV is of public health interest to public health around the world due to our close relationship with animals in agriculture, as companions and in the natural environment. Increasing encroachment on the natural environment is creating more opportunities for zoonotic viruses to cross over into humans.

Dr Simon Scott, from the Viral Pseudotye Unit (VPU) at Medway School of Pharmacy were part of a team led by Dr Gábor Kemenesi from Pécs University/National Laboratory of Virology in Hungary. The VPU were involved in conducting all the antibody detection experiments using bat sera as part of the study, even before the virus itself was isolated. This isolation occurred in the Hungarian lab from the very last bat which tested LLOV positive.

The team discovered that Lloviu has the potential to both infect human cells and replicate, raising concerns about potential widespread transmission in Europe and urges immediate pathogenicity and antiviral studies. The VPU work also revealed no antibody cross-reactivity between LLOV and Ebola, suggesting that existing Ebola vaccines might not protect against Lloviu.

Dr Scott said that their research “is a smoking gun. It’s vital that we know both more about the distribution of this virus and that research is done in this area to assess the risks and to ensure we are prepared for potential epidemics and pandemics.”

The research revealed a considerable knowledge gap regarding the pathogenicity, animal hosts, and transmissibility of these newly discovered viruses. Dr Scott created a consortium of European bat virologists, harnessing expertise in the field, from ecology to virology, which is aiming to carry out essential further research across Europe into the risks of the Lloviu virus to humans.

Source: University of Kent

Ebola Vaccine Instils Lasting Antibody Response

Ebola virus (green) is shown on cell surface.
Credit: National Institutes of Allergy and Infectious Diseases, NIH

A new study has shown that the Ebola vaccine known as rVSVΔG-ZEBOV-GP instils a robust and enduring antibody response among vaccinated individuals in areas of the Democratic Republic of Congo that are experiencing outbreaks of the disease.

The study, published in PNAS, is the first to examine post–Ebola-vaccination antibody response in the DRC, a nation of nearly 90 million. Long-term analyses of the study cohort will continue, but in the meantime, the findings will help inform health officials’ approach to vaccine use for outbreak control, the researchers said.

Ebola, one of the world’s deadliest viral diseases known to infect humans, was first identified in 1976 following an outbreak near the Ebola River in then Zaire (now DRC). Since then, outbreaks have occurred intermittently in sub-Saharan Africa, including 12 outbreaks in the DRC, where the disease remains endemic.

The single-dose rVSVΔG-ZEBOV-GP vaccine was administered to more than 300 000 individuals in the DRC during outbreaks between 2018 and 2020. However, studies examining the antibody response of vaccinated Congolese populations had been lacking.

US and DRC researchers studied individuals who received the vaccine during an Ebola outbreak in the DRC’s North Kivu Province. Between August and September 2018, 608 eligible individuals were vaccinated. In an approach known as “ring vaccination”, these participants were contacts of people infected with Ebola or contacts of those contacts as well as health care and frontline workers in affected or potentially affected areas.
Blood samples were taken at the time of vaccination, 21 days later and again after six months. They found that after 21 days, 87.2% of the study participants showed an antibody response and antibody persistence was seen in 95.6% after six months.

Source: University of California, Los Angeles

Experimental Inhibitor Drug Shows Promise For The Deadly Marburg Virus

Photo by CDC on Unsplash

The lethal Marburg virus, a relative of the Ebola virus, causes a serious haemorrhagic fever with an extremely high fatality rate and has had no known treatment — until now. 

Marburg virus infects human and primates, the disease currently has no approved vaccine or antivirals for prevention or treatment. In two larger recent outbreaks in the DRC in 1998–2000, and in Angola in 2004–2005, Marburg had extremely high fatality rates of 83% and 90%.

A team of researchers is working to change that. In a new paper in the journal Antimicrobial Agents and Chemotherapy, investigators from Penn’s School of Veterinary Medicine, working together with scientists from the Fox Chase Chemical Diversity Center and the Texas Biomedical Research Institute, report encouraging results from tests of an experimental antiviral targeting Marburg virus.

The new compound prevents viruses from leaving infected cells, thus halting the spread of infection. In a first, this new class of inhibitors was shown to be effective against infection in an animal model.

Additionally, possible similarities in virus-host interactions between Marburg and SARS-CoV-2, prompted the team to conducted experiments on the coronavirus. Unpublished preliminary results appeared encouraging.

“It really is exciting. These viruses are quite different but may be interacting with the same host proteins to control efficient egress and spread, so our inhibitors may be able to block them both,” said co-corresponding author Ronald Harty, Professor, Penn’s School of Veterinary Medicine.

Prof Harty’s team have been developing an antiviral that instead of targeting the virus known as “host-oriented.” By blocking the proteins in host cells that viruses hijack during late stages of infection, preventing virus-host interactions.

This method helps prevent a virus evolving resistance, but it also makes it more likely that a drug could be used against multiple viruses, as many make use of the same machinery in the host cell to reproduce and spread.

The Marburg and Ebola viruses use protein known as VP40 to interact with a host protein called Nedd4 to allow the completed viruses to ‘bud off’ of the host cell, which is a key part of viral replication.

Previously, they had tested a variety of small molecule inhibitors of this process using laboratory tests that relied on non-infectious and more-benign viral models. Those assays led them to a promising candidate, FC-10696, for further study.

The researchers firstly tested the chosen inhibitor for safety and its useful duration within the body. Next, since the real Marburg virus is too dangerous to study safely in anything but a Biosafety Level 4 (BSL-4) laboratory, they used an assay to look at what are known as virus-like particles, or VLPs, which are non-infectious but can bud off of a host cell.

Using the Biosafety Level 2 laboratory at Penn, “it’s a very quick way we can test these inhibitors,” said Prof Harty.

The researchers saw a dose-dependent response to FC-10696 on VLP budding in cells tested the compound using the real Marburg virus. These studies were done in a BSL-4 lab at Texas Biomedical Research Institute and found the compound inhibited the budding and spread of live Marburg virus in two human cell types, including in macrophages, an immune cell type commonly infected by the virus.

As a final step, they tested the compound in mice infected with Marburg virus. That received the treatment took longer to display disease symptoms and had a reduced viral load.

“These are the first promising in vivo data for our compounds,” said Prof Harty. “Whereas the control group all became sick very quickly and died, with the treated animals there was one survivor and others showed delayed onset of clinical symptoms. It’s showing that our inhibitors are having an effect.”

Source: News-Medical.Net

Journal information: Han, Z., et al. (2021) Compound FC-10696 Inhibits Egress of Marburg Virus. Antimicrobial Agents and Chemotherapy. doi.org/10.1128/AAC.00086-21.

‘Epidemic Situation’ in Guinea after Cases of Ebola

Recent confirmed cases of an Ebola outbreak have resulted in an epidemic being declared, with governments and health organisations racing to prepare.

After an emergency meeting Sakoba Keita, head of Guinea’s National Health Security Agency, stated: “Very early this morning, the Conakry laboratory confirmed the presence of the Ebola virus.”

In late January, one person had died in Gouécké, near the Liberian border. The victim was buried on 1 February “and some people who took part in this funeral began to have symptoms of diarrhoea, vomiting, bleeding and fever a few days later”, Keita said.

Laboratory testing of samples revealed the presence of Ebola in some of them on Friday, said Keita. He added that, with a total of seven cases and three deaths, Guinea was now in an “Ebola epidemic situation”.

WHO representative Alfred George Ki-Zerbo said in a press briefing: “We are going to rapidly deploy crucial assets to help Guinea, which already has considerable experience [treating the disease]. The arsenal is stronger now and we will take advantage of that to contain this situation as fast as possible.

“The WHO is on full alert and is in contact with the manufacturer [of a vaccine] to ensure the necessary doses are made available as quickly as possible to help fight back.”

Ebola is also flaring up outside of Guinea. On Thursday, the WHO announced a resurgence of Ebola in the DRC, only three months after the outbreak there was declared over. In Guinea’s neighbour Liberia, health authorities have been put on high alert even though no cases have as yet been detected there. 

The deadly Ebola outbreak of 2013-2016 prompted the creation of a global stockpile of 500 000 vaccine doses, which can be drawn upon whenever an outbreak of the disease occurs.

Source: The Guardian

Ebola Vaccine Stockpile Being Created

The International Coordinating Group (ICG) announced on Monday that it was creating a stockpile of the Ebola vaccine in Switzerland, to help contain future outbreaks. Between 2014 and 2016, the haemorrhagic fever claimed 11 300 lives, with a fatality rate of 90%.

The single dose Ebola vaccine was trialled with 350 000 in Guinea and in the 2018-2020 DRC outbreak under “compassionate use”. The vaccine was jointly developed by the World Health Organization (WHO), UNICEF, the International Federation of Red Cross and Red Crescent Societies (IFRC) and Médecins Sans Frontières (MSF), with Gavi, the Vaccine Alliance, providing financial support.Countries requesting a vaccine will be able to receive a response in 48 hours, with a goal for a seven day delivery time.Unlike COVID, Ebola is a rare and unpredictable disease, and thus there is the need to create a reserve for the vaccine as opposed there being a “natural market” for it.

“We are proud to be part of this unprecedented effort to help bring potential Ebola outbreaks quickly under control,” said Henrietta Fore, UNICEF executive director, in a press release, saying that when it comes to dealing with disease outbreaks, “preparedness is key.”

She said the vaccine stash is a “remarkable achievement” that will allow vaccines to be delivered to those who need them in a timely manner. 
Assembling the required 500 000 doses for the stockpile will take some to three years, with 6890 doses currently available for outbreak response. The WHO, UNICEF, Gavi, and vaccine manufacturers are in the meantime are ready to escalate production if needed.

Source: Voice of America News