ARTICLE Issue 018
The Ebola Virus: An Update
In 2010, Sergei Nekhai, Ph.D., professor and vice chair, Department of Medicine, and his team began preliminary research on HIV that eventually produced findings that applied to the Ebola virus, identifying possible inhibitors. That research led to the pursuit of more findings for a more translational research on Ebola inhibitors. Howard's Center for Sickle Cell Disease received nearly $2 million in March 2014 to develop new therapeutics for the Ebola virus infection that will target Ebola virus VP30 protein.
"The overall goal of our studies is to develop a proper inhibitor against the spread of Ebola before and after an individual is infected. While it's not a vaccine, it can be complementary to a possible vaccine and may potentially expand its effectiveness," stated Dr. Nekhai. He and the Howard team, along with their colleagues at the University of Texas, have found one of several candidate molecules that inhibited five Ebola viruses in culture. They are testing whether this and similar molecules inhibit Ebola in mice.
Dr. Gwen Bethea recently interviewed Dr. Nekhai on recent research developments.
Dr. Sergei Nekhai
Dr. Sergei Nekhai, professor and vice chair, Department of Medicine, program director, Center for Hemoglobin Research and chair, Radiation Safety Committee.
Q: What is the Ebola virus?
Nekhai: The Ebola virus is a negative-sense RNA virus, which belongs to the group of Filoviruses. It is named after the Ebola River in the Democratic Republic of Congo where its first outbreak was recorded in 1976. While the Ebola virus only codes for 7 proteins, it is the most deadly virus. Its infection can cause death from hemorrhagic in up to 90% of infected individuals. Luckily, most of the outbreaks happened in very remote areas of the Congo, and did not affect many people. But this is changing with the recent massive outbreak in West Africa (see below). Thus, quick response and improved treatment is needed to contain future outbreaks.
Q: What are the recent developments in Ebola virus research?
Nekhai: There are many developments in Ebola virus research, both on the basic science side and in treatment. There is a better understanding now as to how the virus infects cells by binding to Niemann-Pick C1 protein. There is also better understanding of the mechanisms of viral transcription and viral assembly. Also, structures of many viral proteins were solved, which may help in designing viral inhibitors. Viral pathogenesis is still not fully understood, in part, because Ebola infection of small animals does not fully replicate human infection. Several vaccines were developed and tested during the 2014-2016 outbreak. The vesicle stomatitis virus (VSV)-Ebola virus vaccine was shown to be at least 70 percent efficient, but it is not yet approved by FDA.
Q: What are the connections between HIV-1 and the Ebola virus?
Nekhai: There is no connection between HIV-1 and Ebola virus, except that they are both RNA-containing viruses. Their mechanisms of replication are very different. Despite that, the viruses are likely to use similar host cell proteins for their replication. Our HIV-1 studies pointed to a critical role of host protein phosphatase-1 (PP1) which is needed for efficient HIV-1 transcription and brought to nucleus by HIV-1 Tat protein. Based on these observations, we developed small molecule compounds that inhibited HIV-1 transcription and prevented viral replication in HIV-1 infected humanized mice. Ebola virus transcription, which unlike HIV-1 does not require host polymerase, is regulated by Ebola protein VP30 which can switch viral transcription on and off, depending on its phosphorylation state. We found that PP1 dephosphorylates VP30 in infected cells. We also found that HIV-1 inhibitory small molecules were very efficient in inhibiting Ebola infection in infected cells.
Q: How extensive was the Ebola virus in West Africa; is it on the rise or declining in that location and other locations worldwide? Why or why not?
Nekhai: In a recent 2014-2016 Ebola virus outbreak in West Africa, more than 28,000 people were infected and 11,325 people died from the infection. This was the largest outbreak. This outbreak ended in 2016. There was a recent outbreak in 2017 in Bas Uele District of the Democratic Republic of Congo, with 8 total cases and 4 deaths. While the host for Ebola virus is not fully confirmed, fruit bats are suspected to host the virus. The spread of the Ebola virus from Congo to West Africa was predicted a decade ago based on the spread of fruit bats and the availability of the trees for the bats' nesting. Thus, Ebola virus is likely to reemerge again on the African West Coast where it can again create much causality. The West African countries, such as Liberia and Guinea, are not as well prepared for the infection as the Democratic Republic of Congo. In Congo, there is a history of successful fighting with Small Pox and understanding by local people of the need and efficiency of quarantine. Also, Ebola seems to emerge in remote areas of Congo which helps to contain and quarantine the infection. In contrast, the overpopulated West African countries local populations are at higher risk for Ebola infection and its quick spread. Again, efficient treatment and quick responses are needed to prevent future outbreaks and spread of infection.
Bethea: Thank you.
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