Dudas 2017 Virus genomes reveal factors that spread and sustained the Ebola epidemic The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. hiv Foster_2007 Harold Foster's book on HIV hiv_origin Early AIDS virus may have ridden Africa's rails zoonosis AIDS as a zoonosis: scientific and public health implications. marburg Feldmann_1996 mers Rambut_2015 MERS-CoV potential animal reservoirs and related bat coronaviruses Mackay_2014 Updated MERS-CoV full genome tree Dudas_2017 MERS-CoV spillover at the camel-human interface sars Yount_2006 Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome 2006 usarmy "Three other USAMRIID personnel also have been involved in this ongoing effort: Wes Carter, who traveled with Schoepp to Liberia; Aileen O'Hearn, Ph.D., who recently returned from providing laboratory support to Kenema Government Hospital (KGH) in Sierra Leone; and Matthew Voorhees, who is currently onsite at KGH. USAMRIID has been working in the region since 2006, when it began a collaborative project to develop and refine diagnostic tests for the Lassa fever virus endemic to Sierra Leone, Liberia and Guinea. As those assays have matured, the scientists have begun to optimize additional tests for a number of emerging diseases." ""Prior to the current outbreak, only one case of Ebola had ever been officially reported in this region, and it was from the Ivory Coast strain," said Schoepp. "We were surprised to see that Zaire -- or a variant of Zaire -- was causing infection in West Africa several years ago."" Ahktar et al 2016 Exposing the Origins of the Ebola Outbreak: Urging for a Shift in Response from Reactive to Proactive On August 8, 2014, the World Health Organization established that the current Ebola virus disease (EVD) epidemic is a Public Health Emergency of International Concern (PHEIC), urging the global community to orchestrate their efforts to control the outbreak. As of November 12, 2014 the World Health Organization reported that at least 5,160 lives have been lost to the virus. We conducted a literature review in order to determine the underlying factors contributing to the emergence, rapid spread, and uncontrolled nature of the current virus outbreak, the first to display a distinct epicenter in West Africa. The global community’s reaction to Ebola has been marked by fear. Fear of both the unknown nature of the virus, and knowing that we have made limited efforts in strengthening our arsenal of Ebola fighting treatment options. We explore novel treatment and precautionary approaches in an attempt to shift the response from reactive to proactive in our efforts to battle Ebola. Blackley 2016 On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over. Gire 2014 Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak "One notable intrahost variation is the RNA editing site of the glycoprotein (GP) gene which we characterized in patients" "The RNA editing site of the glycoprotein (GP) gene consists of 7 U residues; cotranscriptional stuttering can result in transcripts with more or less A residues. The resulting frameshifts allow for the expression of distinct glycoproteins called sGP (7 A), GP (predominantly 8 A), and ssGP (predominantly 6 A). Previous studies have demonstrated that EBOV passaging results in distinct changes in the genomic editing site, which switches to 8 U in tissue culture and to 7 U in infected guinea pigs and nonhuman primates, and thereby in different ratios of edited transcripts. Deep sequencing revealed 8 U at ~ 1% and 7 U at ~ 99% (fig. S5B). This differs from the proportions previously reported in animal models and tissue culture (8 U 20%; 7 U 80%) (12, 19) and represents the first measurement of these intrahost ratios in an unpassaged (p0) isolate and in a human outbreak setting. Caution is needed in comparing these differences, however, since the previous studies were performed using cloning-based Sanger sequencing." SupplementalEbola Genomic materials and cladograms can be found at the link. "Molecular dating places the common ancestor of all sequenced Guinea and Sierra Leone lineages around late February 2014" Hoenen 2015 Mutation rate and genotype variation of Ebola virus from Mali case sequences The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns. Holmes 2017 The Evolution of Ebola virus: Insights from the 2013–2016 Epidemic "Molecular clock dating analyses have also shown that all recorded human EVD outbreaks caused by EBOV appear to share a common ancestor around 1975"

Kaner 2014 Understanding Ebola: the 2014 epidemic The standard treatment for Ebola patients has not changed in the last 50 years and consists of symptomatic and supportive care [24]. Supportive care involves either oral or intravenous rehydration and electrolyte management; while symptomatic care involves the use of drugs to reduce vomiting and diarrhea, along with medication to treat fever and pain [32–34]. Patients with high malaria risk are also given anti-malarial medication and antibiotics to preemptively treat common infections that may hamper their ability to fight Ebola. Currently, drugs being developed to treat Ebola work by inhibiting viral replication either by targeting viral transcripts for degradation, blocking translation, or acutely neutralizing the virus [35]. Other treatments that are being studied include passive immunotherapy (blood transfusion from survivors) and mechanical filtering of patient blood [36, 37]. Kuhn 2010 Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations Abstract The taxonomy of the family Filoviridae (marburgviruses and ebolaviruses) has changed several times since the discovery of its members, resulting in a plethora of species and virus names and abbreviations. The current taxonomy has only been partially accepted by most laboratory virologists. Confusion likely arose for several reasons: species names that consist of several words or which (should) contain diacritical marks, the current orthographic identity of species and virus names, and the similar pronunciation of several virus abbreviations in the absence of guidance for the correct use of vernacular names. To rectify this problem, we suggest (1) to retain the current species names Reston ebolavirus, Sudan ebolavirus, and Zaire ebolavirus, but to replace the name Cote d'Ivoire ebolavirus [sic] with Taï Forest ebolavirus and Lake Victoria marburgvirus with Marburg marburgvirus; (2) to revert the virus names of the type marburgviruses and ebolaviruses to those used for decades in the field (Marburg virus instead of Lake Victoria marburgvirus and Ebola virus instead of Zaire ebolavirus); (3) to introduce names for the remaining viruses reminiscent of jargon used by laboratory virologists but nevertheless different from species names (Reston virus, Sudan virus, Taï Forest virus), and (4) to introduce distinct abbreviations for the individual viruses (RESTV for Reston virus, SUDV for Sudan virus, and TAFV for Taï Forest virus), while retaining that for Marburg virus (MARV) and reintroducing that used over decades for Ebola virus (EBOV). Paying tribute to developments in the field, we propose (a) to create a new ebolavirus species (Bundibugyo ebolavirus) for one member virus (Bundibugyo virus, BDBV); (b) to assign a second virus to the species Marburg marburgvirus (Ravn virus, RAVV) for better reflection of now available high-resolution phylogeny; and (c) to create a new tentative genus (Cuevavirus) with one tentative species (Lloviu cuevavirus) for the recently discovered Lloviu virus (LLOV). Furthermore, we explain the etymological derivation of individual names, their pronunciation, and their correct use, and we elaborate on demarcation criteria for each taxon and virus. Ladner 2015 Evolution and Spread of Ebola Virus in Liberia, 2014–2015 Smits 2015 Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015 The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H.sapienswt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus. army statement SL Army Scientist Uses Diagnostic Tools to Track Viruses "FORT DETRICK, Md., Dec. 17, 2014 — An Army virologist using diagnostic tools found traces of Ebola virus in patient samples in West Africa -- a region thought to be untouched by the disease -- seven years before the largest, deadliest Ebola outbreak took the world by surprise in Guinea, Liberia and Sierra Leone." "In 2006, Schoepp was working in Sierra Leone at the Kenema Government Hospital in Eastern Province, helping a collaboration of USAMRIID and Tulane University scientists who were there to develop and refine Lassa fever diagnostic tests and build host-country diagnostic capacity." "“One reason I was interested in Sierra Leone is because, for those of us who work with hemorrhagic fevers … this is the only place you can study them because you know they’re going to show up and you know where they’re going to be,” the virologist said." "IgM is the first antibody to be made by the body to fight a new infection, Schoepp said, “so if you find IgM antibodies it tells you that you're very close to the original infection.” Looking further into the Ebola antibodies with the plaque reduction neutralization test, which many scientists consider the "gold standard" for detecting and measuring antibodies that can neutralize many disease-causing viruses, Schoepp saw that most of the Ebola antibodies were against the Zaire strain. Ebola Zaire is the most virulent of the virus’s five strains, Schoepp said, and the one that is now causing the West African outbreak. In a region supposedly untouched by Ebola except for a single case of the Tai Forest strain reported in Cote d’Ivoire in 1994, Schoepp said, this was big news that at the time could have been unwelcome in the three countries." Afterward, in August 2013, he submitted a scientific paper about the West African Ebola finding to CDC’s Emerging Infectious Diseases journal. After nearly a year and reviews by two sets of scientists, the final reviewer told Schoepp, “I don’t believe there is Ebola virus in West Africa.” A week later, Schoepp said, the West African Ebola outbreak was announced to the world and, after an email from Schoepp to the journal editor, “Undiagnosed Acute Viral Febrile Illnesses, Sierra Leone,” was published in July 2014. “To me, it means that there is more Ebola out in the world than you would know by past outbreaks or by other evidence,” Schoepp said, discussing the paper’s results. “If you look for it, you have a very good chance of finding it.” Diagnostics, he added, is the basis of everything. “We set the stage for others to come in and do their therapeutics, their antivirals, their vaccines,” Schoepp said. “Knowing what's there is one thing, and being able to do something about what's there is another thing. So diagnostics gives the epidemiologists, immunologists and the therapeutic people something to do.” In a time when globalization spreads diseases farther and faster than ever (emph. mine - RJS), Schoepp said, it’s a good time to be a virologist. See also "The study will enroll adult volunteers who present as severely ill with a suspected infectious source. In addition to receiving the usual care for their illness, they will be asked to provide samples for laboratory analysis and to complete a brief questionnaire that captures basic clinical, demographic and exposure data." se bad Selenium Deficiency and Viral Infection "More recent research has shown that a mild strain of influenza virus, influenza A/Bangkok/1/79, also exhibits increased virulence when given to Se-deficient mice. This increased virulence is accompanied by multiple changes in the viral genome in a segment previously thought to be relatively stable. Epidemic neuropathy in Cuba has features that suggest a combined nutritional/viral etiology" This explains how the REBOV which does not encode for selenium and is harmless probably mutated into ZEBOV which does and this had to happen in a high selenium area such as Gabon. The most likely place for an outbreak given parameters of soil and population growth could be Kinshasa/Zaire, notoriously low in selenium and the hub of economic growth in that area. It is probably no coincidence that HIV was found to originate there, except that it could not have. A selenium containing virus can not evolve in an area of no selenium and it almost certainly originated i the jungles of west Africa. In fact the species of Ape (Pan troglodytes) has been identified and their range is West Africa to the Congo. se found A Basis for New Approaches to the Chemotherapy of AIDS: Novel Genes in HIV-1 Potentially Encode Selenoproteins Expressed by Ribosomal Frameshifting and Termination Suppression Selenium found in viral DNA. taylor Selenium Against Viruses: More Exciting Research from Dr. Will Taylor "Similarly, we have now demonstrated GPx-like sequences in Coxsackie B virus, the viral cofactor for Keshan disease, and the subject of the now famous Levander and Beck studies." "I am referring to the use of selenium to treat an Ebola-like hemorrhagic fever that broke out in China in the late 1980s. Hemorrhagic fevers can kill up to 90 percent of those infected, but this study showed that selenium supplementation can reduce that mortality rate dramatically." us army USAMRIID supports Ebola Virus Disease outbreak response in West Africa is region, and it was from the Ivory Coast strain," said Schoepp. "We were surprised to see that Zaire -- or a variant of Zaire -- was causing infection in West Africa several years ago."We were surprised to see that Zaire -- or a variant of Zaire -- was causing infection in West Africa several years ago. zaire Theoretical Evidence that the Ebola Virus Zaire Strain May Be Selenium-Dependent: A Factorin Pathogenesis and Viral Outbreaks? 1995: Ethan Will Taylor and Chandra Sekar Ramanathan