UCSC Ebola Genome Portal Resources for the 2014 West Africa Outbreak

About

The 2014 Ebola epidemic in West Africa has stirred international response and renewed efforts to develop effective preventative and treatment options. In response to a request for help from vaccine researchers, we have fast-tracked the UCSC Ebola Genome Browser built with viral sequences from previous outbreaks as well as the 2014 outbreak. This site also provides related tools and information that can be used to further the understanding of Ebola.

Explore the Ebola Genome with the UCSC Browser

Learn about the 2014 outbreak

Read about Ebola

Related Publications and Data Resources

PLOS Ebola Flipboard: PLOS Ebola Collection (all currently published articles, freely available)

Science Magazine collection: Science Magazine Special Collection: Ebola Virus (freely available research and news articles)

NCBI sequence database search, publication list, and genome display: NCBI Virus Variation Ebolavirus Resource

The New England Journal of Medicine resource: Ebola Outbreak (A collection of articles and other resources on the Ebola outbreak, including clinical reports, management guidelines, and commentary.)

Ebola Biology

Ebola virus is the causative agent of Ebola hemorrhagic fever (EHF), a disease affecting humans and other primates. The incubation period for EHF is 2-21 days and typical early symptoms include fever, chills, malaise, and myalgia, followed by the onset of symptoms indicative of multi-organ stress and subsequent failure. The disease is also characterized by high death rates (as high as 90%) and worse yet, is highly contagious, spreading through direct contact with infected body fluids or skin/mucus membrane contact. This perfect storm of conditions make the possibility of a large-scale epidemic a very real concern.

Ebola virus and the related Marburg virus are members of the family Filoviridae, so named for their filamentous shape. Like other Filoviruses, Ebola is an enveloped, non-segmented, negative-stranded RNA virus. Ebola virus particles have at their core a viral nucleocapsid composed of a helical single stranded RNA genome wrapped around viral proteins NP, VP35, VP30, and L. The nucleocapsid is surrounded by an outer viral envelope studded with viral glycoprotein (GP) spikes, and viral proteins VP40 and VP24 sit between the nucleocapsid and the envelope.

The viral life cycle begins with host cell entry through a poorly understood mechanism. Once inside the viral RNA-dependent RNA polymerase (L) binds the 19 kb genome as a complex with other factors and transcribes the negative strand genome into a positive strand mRNA to be translated by the host cell's machinery. The seven genes are ordered in the genome as follows: 3-leader-NP-VP35-VP40-GP/sGP-VP30-VP24-L-trailer-5'. Once the concentration of nucleocapsid protein (NP) reaches a sufficient level, the RNA polymerase switches modes to genome replication, producing full-length positive strand genomes to be transcribed into negative orientation. These genomes self assemble with other virus proteins and bud from the host cell, sheathed in host cell membrane, thus completing the cycle.

Vaccine Development

In September 2014, Phase 1 clinical trials of the GlaxoSmithKline ChAd3/EBOV vaccine began at the U.S. National Institutes of Health and UK Oxford, and a second vaccine (VSV/EBOV, produced by Newlink Genetics) was approved for trial by the U.S. FDA. If the vaccines are found to be safe, some doses could be available for use by healthcare workers in November.

Other vaccines have been tested in non-human primates with good results. Ebola mutates slower than many viruses (e.g. HIV) and is considered a good vaccine target. We have collected some review articles and research reports pertaining to Ebola vaccine development here: Ebola Vaccine Development: Scientific References.

A vaccine will do much to slow the spread of this epidemic. After preliminary safety trials the question becomes how fast production can be scaled, which is contingent on funding. At this time, GlaxoSmithKline has committed to the production of 10,000 vaccine doses by year's end. With the U.S. committing significant federal funds to the fight against Ebola, we can hope that vaccines will be available in quantity. From Marie-Paule Kieny, assistant director-general of WHO, who spoke at a press conference in Geneva in early September: "There is a tide in the affairs of men, and that tide is now."

Treatment Research

Multiple therapeutic approaches for Ebola treatment are under active development. References for three close to field use as of September 2014 are listed below. See also the CDC Questions and Answers on Experimental Treatments and Vaccines for Ebola.

Lamivudine : A nucleoside analog reverse transcriptase inhibitor being sold across Africa as an HIV drug. It has shown remarkable efficacy against the Ebola virus.

AVI-7537 : A drug designed to inhibit the synthesis of nucleocapsid proteins by Sarepta Therapeutics.

Broad-spectrum small molecule anti-viral: Inhibition of viral RNA polymerase by other nucleoside analogues

RNA interference: Combination of siRNAs targeting Ebolavirus RNA polymerase and other proteins (e.g. VP24 and VP35)

Immunologic: Cocktail of neutralizing antibodies specific for Ebolavirus surface glycoprotein

Additional references related to Ebola antibody-based therapeutics are listed at: UCSC Ebola Genome Portal: Antibody Resources.