Reston ebolavirus | |
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An artificially colored transmission electron micrograph of the Reston virus | |
Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Negarnaviricota |
Class: | Monjiviricetes |
Order: | Mononegavirales |
Family: | Filoviridae |
Genus: | Ebolavirus |
Species: | Reston ebolavirus |
Synonyms | |
Reston virus (RESTV) |
Reston virus (RESTV) is one of six known viruses within the genus Ebolavirus . Reston virus causes Ebola virus disease in non-human primates; out of all 6 ebolaviruses, it is one of the only two not known to cause disease in humans, but has caused asymptomatic infections. [1] [2] [3] Reston virus was first described in 1990 as a new "strain" of Ebola virus (EBOV). [4] It is the single member of the species Reston ebolavirus, which is included into the genus Ebolavirus , family Filoviridae , order Mononegavirales . [5] Reston virus is named after Reston, Virginia, US, where the virus was first discovered.
RESTV was discovered in crab-eating macaques imported by Hazleton Laboratories (now Fortrea) in 1989. This attracted significant media attention due to Reston's location in the Washington metropolitan area and the lethality of a closely related Ebola virus. Despite its status as a level-4 organism, Reston virus is non-pathogenic to humans, though hazardous to monkeys; [6] [7] the perception of its lethality was compounded by the monkey's coinfection with Simian hemorrhagic fever virus (SHFV). [8] Despite ongoing research, the determinants for lack of human pathogenicity are yet to be discovered. [9]
Reston virus was first introduced as a new "strain" of Ebola virus in 1990. [4] In 2000, it received the designation Reston Ebola virus [10] [11] and in 2002, the name was changed to Reston ebolavirus. [12] [13] Previous abbreviations for the virus were EBOV-R (for Ebola virus Reston) and most recently REBOV (for Reston Ebola virus or Reston ebolavirus). The virus received its current designation in 2010, when it was renamed Reston virus (RESTV). [5]
A virus of the species Reston ebolavirus is a Reston virus (RESTV) if it has the properties of Reston ebolaviruses and if its genome diverges from that of the prototype Reston virus. For example, there exists Reston virus variant Pennsylvania (RESTV/Pen), differing by less than 10% at the nucleotide level. [5]
While investigating an outbreak of Simian hemorrhagic fever (SHFV) in November 1989, an electron microscopist from USAMRIID named Thomas W. Geisbert discovered filoviruses similar in appearance to Ebola virus in tissue samples taken from a crab-eating macaque imported from the Philippines to a facility operated by Hazleton Laboratories (now Fortrea) in Reston, Virginia. The filovirus was further isolated by Dr. Peter Jahrling, and over the period of three months over a third of the monkeys died—at a rate of two or three a day. [14]
Blood samples were taken from 178 animal handlers during the incident. [15] Of them, six eventually seroconverted, testing positive using ELISA. They remained, however, asymptomatic. In January 1990, an animal handler at Hazleton cut himself while performing a necropsy on the liver of an infected Cynomolgus. Under the direction of the Centers for Disease Control and Prevention (CDC), the animal handler was placed under surveillance for the duration of the incubation period. When the animal handler failed to become ill, it was concluded that the virus had a low pathogenicity in humans. [16]
Following the discovery of a filovirus in crab-eating macaques, an investigation tracing the infection was conducted by the CDC. The monkeys were imported from the Philippines, which had no previous record of SHFV or ebolavirus infections. It was suspected that the monkeys contracted both diseases while in transit aboard KLM Airlines before reaching Reston. Shipments were tracked to New York City, Texas, and Mexico City, none of which produced cases of infection. [17]
By January 1990, Hazleton Laboratories recovered from its previous losses and began importing monkeys again from the same establishment in Manila that had provided the original animals. The imported monkeys became infected and were euthanized. [15] In early February the CDC received reports of the disease in Alice, Texas. In March, the Division of Quarantine at the CDC secured a temporary ban on the importation of monkeys into the United States from anywhere in the world. [18]
Following the announcement of the filovirus disease outbreak in Reston, Virginia, a serosurvey was conducted to assess the prevalence of the infection. Of the several hundred serums received by the CDC, approximately ten percent showed some reaction to ebolavirus antigen—though usually at low levels. Counterintuitively, the majority of the monkeys found positive were from Indonesia. [19]
In May 1990, an investigation led by Susan Fisher-Hoch, Steve Ostroff, and Jerry Jennings was sent to Indonesia. During the investigation, it was hypothesized that there could be a cross infection since monkeys suspected of illness were typically placed in gang cages containing up to twenty to thirty other monkeys suspected of illness. Upon arrival they were told that most of the monkeys were imported from the island of Sumatra. The investigation team found no trace of the virus in either case. [20]
Following the investigation in Indonesia, an experiment was conducted in the level-4 lab at the CDC campus in DeKalb County, Georgia with thirty-two monkeys: sixteen green monkeys (Cercopithecus aethiops) and sixteen crab-eating macaques. Half of the sixteen green monkeys and crab-eating macaques were infected with Reston virus and the other half with Ebola virus. Ebola virus infection was lethal to nearly all monkeys. However, most of the monkeys infected with Reston virus recovered in a month. The surviving monkeys were kept for two years to detect any trace of the virus - none was found. However, the monkeys continued to possess a high level of antibody. [8]
Following the test at the CDC campus in DeKalb County, two of the monkeys who had survived Reston virus infection were infected with a very large dose of the Ebola virus in an effort to produce an Ebola vaccine. One of the two monkeys remained resistant; the second died. [8]
The physical building in which the outbreak occurred was demolished on 30 May 1995 and a daycare center was constructed in its place. [21] Modern spatial computer simulation indicates that the pathogen could have reached both major airports (Dulles International Airport and Ronald Reagan Washington National Airport) in less than 45 minutes assuming direct transmission paths. [22]
Marburg virus disease (MVD), formerly Marburg hemorrhagic fever (MHF) is a viral hemorrhagic fever in human and non-human primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).
Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.
The genus Marburgvirus is the taxonomic home of Marburg marburgvirus, whose members are the two known marburgviruses, Marburg virus (MARV) and Ravn virus (RAVV). Both viruses cause Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. Both are select agents, World Health Organization Risk Group 4 Pathogens, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogens, Centers for Disease Control and Prevention Category A Bioterrorism Agents, and are listed as Biological Agents for Export Control by the Australia Group.
The genus Ebolavirus is a virological taxon included in the family Filoviridae, order Mononegavirales. The members of this genus are called ebolaviruses, and encode their genome in the form of single-stranded negative-sense RNA. The six known virus species are named for the region where each was originally identified: Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Taï Forest ebolavirus, Zaire ebolavirus, and Bombali ebolavirus. The last is the most recent species to be named and was isolated from Angolan free-tailed bats in Sierra Leone. Each species of the genus Ebolavirus has one member virus, and four of these cause Ebola virus disease (EVD) in humans, a type of hemorrhagic fever having a very high case fatality rate. The Reston virus has caused EVD in other primates. Zaire ebolavirus has the highest mortality rate of the ebolaviruses and is responsible for the largest number of outbreaks of the six known species of the genus, including the 1976 Zaire outbreak and the outbreak with the most deaths (2014).
The Hot Zone: A Terrifying True Story is a best-selling 1994 nonfiction thriller by Richard Preston about the origins and incidents involving viral hemorrhagic fevers, particularly ebolaviruses and marburgviruses. The basis of the book was Preston's 1992 New Yorker article "Crisis in the Hot Zone".
Mayinga N'Seka was a nurse in Zaïre, now Democratic Republic of the Congo. She died from Ebola virus disease during the 1976 epidemic in Zaïre. She has been incorrectly identified as the index case by several sources, but a World Health Organization commission report on the outbreak lists a man from Yambuku, Mabalo Lokela, as the index case. Lokela, a 44-year-old who had been buying meat in Sudan, died on September 8, 1976, over a month before N'Seka.
Lisa Ellen Hensley is the associate director of science at the Office of the Chief Scientist, National Institute of Allergy and Infectious Disease Integrated Research Facility in Frederick, Maryland. She was previously a civilian microbiologist in the virology division of the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Hensley is one of the premier researchers of some of the world's most dangerous infections, including Ebola hemorrhagic fever, Lassa fever, the coronavirus diseases Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and smallpox. She has been involved in research uncovering critical mechanisms in the pathogenesis of hemorrhagic fever viruses, and has used those discoveries to develop candidate therapeutic drugs for their treatment.
The species Lloviu cuevavirus is the taxonomic home of a virus that forms filamentous virion, Lloviu virus (LLOV). The species is included in the genus Cuevavirus. LLOV is a distant relative of the commonly known Ebola virus and Marburg virus.
The species Bundibugyo ebolavirus is the taxonomic home of one virus, Bundibugyo virus (BDBV), that forms filamentous virions and is closely related to the infamous Ebola virus (EBOV). The virus causes severe disease in humans in the form of viral hemorrhagic fever and is a Select agent, World Health Organization Risk Group 4 Pathogen, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and is listed as a Biological Agent for Export Control by the Australia Group.
The species Taï Forest ebolavirus is a virological taxon included in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The species has a single virus member, Taï Forest virus (TAFV). The members of the species are called Taï Forest ebolaviruses.
The species Sudan ebolavirus is a virological taxon included in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The species has a single virus member, Sudan virus (SUDV). The members of the species are called Sudan ebolaviruses. It was discovered in 1977 and causes Ebola clinically indistinguishable from the ebola Zaire strain, but is less transmissible than it. Unlike with ebola Zaire there is no vaccine available.
Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.
Ravn virus is a close relative of Marburg virus (MARV). RAVV causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever. RAVV is a Select agent, World Health Organization Risk Group 4 Pathogen, National Institutes of Health/National Institute of Allergy and Infectious Diseases Category A Priority Pathogen, Centers for Disease Control and Prevention Category A Bioterrorism Agent, and listed as a Biological Agent for Export Control by the Australia Group.
Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after infection. The first symptoms are usually fever, sore throat, muscle pain, and headaches. These are usually followed by vomiting, diarrhoea, rash and decreased liver and kidney function, at which point some people begin to bleed both internally and externally. It kills between 25% and 90% of those infected – about 50% on average. Death is often due to shock from fluid loss, and typically occurs between six and 16 days after the first symptoms appear. Early treatment of symptoms increases the survival rate considerably compared to late start. An Ebola vaccine was approved by the US FDA in December 2019.
Zaire ebolavirus, more commonly known as Ebola virus, is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and was the cause of the 2013–2016 epidemic in western Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths.
ZMapp is an experimental biopharmaceutical medication comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. Two of the three components were originally developed at the Public Health Agency of Canada's National Microbiology Laboratory (NML), and the third at the U.S. Army Medical Research Institute of Infectious Diseases; the cocktail was optimized by Gary Kobinger, a research scientist at the NML and underwent further development under license by Mapp Biopharmaceutical. ZMapp was first used on humans during the Western African Ebola virus epidemic, having only been previously tested on animals and not yet subjected to a randomized controlled trial. The National Institutes of Health (NIH) ran a clinical trial starting in January 2015 with subjects from Sierra Leone, Guinea, and Liberia aiming to enroll 200 people, but the epidemic waned and the trial closed early, leaving it too statistically underpowered to give a meaningful result about whether ZMapp worked.
Galidesivir is an antiviral drug, an adenosine analog. It was developed by BioCryst Pharmaceuticals with funding from NIAID, originally intended as a treatment for hepatitis C, but subsequently developed as a potential treatment for deadly filovirus infections such as Ebola virus disease and Marburg virus disease, as well as Zika virus. Currently, galidesivir is under phase 1 human trial in Brazil for coronavirus.
Ansuvimab, sold under the brand name Ebanga, is a monoclonal antibody medication for the treatment of Zaire ebolavirus (Ebolavirus) infection.
A Marburg vaccine would protect against Marburg virus disease (MVD). There are currently no Food and Drug Administration-approved vaccines for the prevention of MVD. Many candidate vaccines have been developed and tested in various animal models. There is not yet an approved vaccine, because of economic factors in vaccine development, and because filoviruses killed few before the 2010s.