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Disease Biomarkers Seen 4 Days BEFORE Ebola Sympom

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    Posted: March 28 2018 at 3:03pm

Don't Panic - nothing nasty happening - Just research


Potential biomarkers in animals could signal Ebola virus infection before symptoms appear

March 28, 2018

Scientists have identified potential biomarkers in nonhuman primates exposed to Ebola virus (EBOV) that appeared up to four days before the onset of fever, according to research published today in the journal Science Translational Medicine.

The work, a collaboration between the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and Boston University (BU), could pave the way for developing diagnostic tools to identify EBOV infection in humans even before symptoms appear. Such tools would be invaluable in limiting the spread of disease where there are cases of known potential exposure to the virus, according to USAMRIID investigator Sandra L. Bixler, Ph.D., the paper's co-first author.

Bixler said previously developed animal models of EBOV infection have an acute disease course lasting only 7-10 days on average. This makes therapeutic intervention challenging, since the timeframe for administering treatment is very short. In addition, such models are based on high viral doses and are uniformly lethal, which does not reflect the variable and comparatively extended time to disease onset seen in humans.

"Those models make sense for testing vaccines and therapeutics," Bixler commented. "But for human infection, they don't really match what we see in the field -- especially given what we've learned from the most recent Ebola virus disease outbreak in Western Africa."

So Bixler and USAMRIID colleague Arthur J. Goff, Ph.D., decided to investigate alternative models that could still replicate human infection while extending the disease course. Instead of challenging the animals via injection, which is a standard laboratory model, they tested the intranasal route -- which would be more likely to occur in a natural outbreak where people may be exposed to infected bodily fluids.

The team designed a study using a lower dose of EBOV in 12 cynomolgus macaques. The animals, exposed by intranasal infection and closely monitored for signs of disease, fell into four categories. Three succumbed to disease in the usual timeframe of 7-10 days following infection; four had a delayed onset of 10-15 days; three were late-onset (20-22 days); and two survived.

"We were then faced with the challenge of teasing apart any differences between acute versus delayed disease onset, and survivors versus non-survivors," said Louis A. Altamura, Ph.D., one of the USAMRIID scientists who performed gene expression profiling to monitor the host response via changes in RNA transcripts over time. Thanks to a long-standing collaboration between USAMRIID and BU, investigators at USAMRIID's Center for Genome Sciences, along with BU scientists John H. Connor, Ph.D., and Emily Speranza, Ph.D., performed further genomic data analysis and began to look for early markers of infection.

What they found -- in all the animals except the two survivors -- were interferon-stimulating genes that appear prior to infection with Ebola virus. Importantly, the genes can be detected four days before the onset of fever, which is one of the earliest clinical signs of EBOV exposure. When Speranza compared the results to humans, using Ebola patient blood samples from the most recent outbreak, she found the same pattern.

"This demonstrates that lethal Ebola virus disease has a uniform and predictable response to infection, regardless of the time to onset," commented Gustavo Palacios, Ph.D., who directs USAMRIID's Center for Genome Sciences. "Furthermore, expression of a subset of genes could predict disease development prior to other host-based indications of infection, such as fever."

EBOV causes severe hemorrhagic fever in humans and nonhuman primates with high mortality rates and continues to emerge in new geographic locations, including Western Africa, the site of the largest recorded outbreak to date. More than 28,000 confirmed, probable and suspected cases have been reported in Guinea, Liberia and Sierra Leone, with more than 11,000 reported deaths, according to the World Health Organization (WHO). Today, WHO estimates that there are over 10,000 survivors of Ebola virus disease.

Research on Ebola virus is conducted under Biosafety Level 4, or maximum containment conditions, where investigators wear positive-pressure "space suits" and breathe filtered air as they work. USAMRIID is the only laboratory in the Department of Defense with Biosafety Level 4 capability, and its research benefits both military personnel and civilians.


Source of Research:  US Army Medical Research Institute of Infectious Diseases

My Source:  https://www.sciencedaily.com/releases/2018/03/180328143258.htm

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Not only has diagnosis improved, there may soon be a treatment too:

Chemical compound inhibits Ebola virus replication

Date:
March 28, 2018
Source:
Georgia State University
Summary:
An organic chemical compound shows effective antiviral activity against Ebola virus and several other viruses, according to a new study.

FULL STORY

An organic chemical compound shows effective antiviral activity against Ebola virus and several other viruses, according to a study led by Georgia State University.

The researchers found benzoquinoline inhibited the ability of Ebola virus to multiply and reproduce in cell culture. The findings are published in the journal Antiviral Research.

Ebola virus, a member of the filovirus family, is an enveloped, single-stranded RNA virus that causes severe disease in humans. The largest outbreak on record for the filovirus family was caused by Ebola virus in West Africa between 2013 and 2016, resulting in more than 28,000 infections and more than 11,000 deaths.

Only experimental treatments were available, and survivors, including health care workers, are at risk for persistent infections from the virus remaining in sites that can tolerate foreign substances without eliciting an inflammatory immune response, such as the eye and testes. There are no approved drugs to treat Ebola virus or other filovirus infections, so there is a critical need for new therapeutic approaches. A potential antiviral target is the viral machinery and activities involved in carrying out RNA synthesis for Ebola virus.

"This work provides a foundation for the development of novel antiviral agents to combat Ebola virus," said Dr. Christopher Basler, director of the Center for Microbial Pathogenesis and professor in the Institute for Biomedical Sciences at Georgia State and a Georgia Research Alliance Eminent Scholar in Microbial Pathogenesis.

In this study, the researchers screened a library of 200,000 small molecule compounds to identify potential inhibitors of Ebola virus RNA synthesis. They identified 56 hits that inhibited Ebola virus activity by more than 70 percent, while showing less than a 20 percent chance of being toxic to cells. They discovered three chemical structures with potent antiviral activity against Ebola virus in cell culture.

Human lung epithelial cells and human embryonic kidney cells were exposed to several viruses, Ebola virus, Marburg virus, vesicular stomatitis virus and Zika virus, and the antiviral effects of the three chemical structures were observed.

One of these chemical structures, benzoquinoline, showed antiviral activity against Ebola virus and was also active against another deadly filovirus, Marburg virus. Benzoquinoline was also effective against vesicular stomatitis virus from the rhabdovirus family, which can infect insects, cattle, horses and pigs, and Zika virus, which is spread to humans by mosquitoes.

"This study is part of a larger effort to find new therapies to treat highly dangerous Ebola virus infections," said lead author Dr. Priya Luthra of Georgia State.


Story Source:

Materials provided by Georgia State University. Note: Content may be edited for style and length.


Journal Reference:

  1. Priya Luthra, Jue Liang, Colette A. Pietzsch, Sudip Khadka, Megan R. Edwards, Shuguang Wei, Sampriti De, Bruce Posner, Alexander Bukreyev, Joseph M. Ready, Christopher F. Basler. A high throughput screen identifies benzoquinoline compounds as inhibitors of Ebola virus replication. Antiviral Research, 2018; 150: 193 DOI: 10.1016/j.antiviral.2017.12.019

My source:   https://www.sciencedaily.com/releases/2018/03/180328182455.htm


Absence of proof is not proof of absence.
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