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Reston virus (RESTV) is one of six known viruses within the
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
''
Ebolavirus The genus ''Ebolavirus'' (- or ; - or ) is a International Committee on Taxonomy of Viruses, virological taxon included in the family ''Filoviridae'' (filament-shaped viruses), order ''Mononegavirales''. The members of this genus are called ebo ...
''. Reston virus causes
Ebola virus disease 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 infe ...
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. Reston virus was first described in 1990 as a new "strain" of
Ebola virus ''Orthoebolavirus zairense'' or Zaire ebolavirus, more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal vira ...
(EBOV). It is the single member of the
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
''Reston ebolavirus'', which is included into the
genus Genus (; : genera ) is a taxonomic rank above species and below family (taxonomy), family as used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In bino ...
''
Ebolavirus The genus ''Ebolavirus'' (- or ; - or ) is a International Committee on Taxonomy of Viruses, virological taxon included in the family ''Filoviridae'' (filament-shaped viruses), order ''Mononegavirales''. The members of this genus are called ebo ...
'',
family Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...
''
Filoviridae ''Filoviridae'' () is a International Committee on Taxonomy of Viruses, family of RNA virus#Group_V_–_negative-sense_ssRNA_viruses, single-stranded negative-sense RNA viruses in the order (biology), order ''Mononegavirales''. Two members of the ...
'',
order Order, ORDER or Orders may refer to: * A socio-political or established or existing order, e.g. World order, Ancien Regime, Pax Britannica * Categorization, the process in which ideas and objects are recognized, differentiated, and understood ...
''
Mononegavirales ''Mononegavirales'' is an order of negative-strand RNA viruses which have nonsegmented genomes. Some members that cause human disease in this order include Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah viru ...
''. Reston virus is named after
Reston, Virginia Reston is a census-designated place in Fairfax County, Virginia, United States, and a principal city of both Northern Virginia and the Washington metropolitan area. As of the 2020 U.S. census, Reston's population was 63,226. Founded in 1964, Rest ...
, US, where the virus was first discovered. RESTV was discovered in
crab-eating macaque The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settlem ...
s imported by Hazleton Laboratories (now Fortrea) in 1989. This attracted significant media attention due to Reston's location in the
Washington metropolitan area The Washington metropolitan area, also referred to as the National Capital Region, Greater Washington, or locally as the DMV (short for Washington, D.C., District of Columbia, Maryland, and Virginia), is the metropolitan area comprising Washing ...
and the lethality of a closely related Ebola virus. Despite its status as a level-4 organism, Reston virus is non-
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
ic to humans, though hazardous to monkeys; the perception of its lethality was compounded by the monkey's
coinfection Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with hepatit ...
with Simian hemorrhagic fever virus (SHFV). Despite ongoing research, the determinants for lack of human pathogenicity are yet to be discovered.


Nomenclature

Reston virus was first introduced as a new "strain" of Ebola virus in 1990. In 2000, it received the designation Reston Ebola virus and in 2002, the name was changed to Reston ebolavirus. 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). A virus of the species ''Reston ebolavirus'' is a Reston virus (RESTV) if it has the properties of
Reston ebolavirus 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 ca ...
es and if its
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
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 Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
level.


History


Discovery

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 ''Orthoebolavirus zairense'' or Zaire ebolavirus, more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal vira ...
in tissue samples taken from a
crab-eating macaque The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settlem ...
imported from the
Philippines The Philippines, officially the Republic of the Philippines, is an Archipelagic state, archipelagic country in Southeast Asia. Located in the western Pacific Ocean, it consists of List of islands of the Philippines, 7,641 islands, with a tot ...
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. Blood samples were taken from 178 animal handlers during the incident. Of them, six eventually seroconverted, testing positive using
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
. 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 The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settleme ...
. Under the direction of the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
(CDC), the animal handler was placed under surveillance for the duration of the
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...
. When the animal handler failed to become ill, it was concluded that the virus had a low
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
icity in humans.


Investigation

Following the discovery of a
filovirus ''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 rela ...
in crab-eating macaques, an investigation tracing the infection was conducted by the
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
. The monkeys were imported from the
Philippines The Philippines, officially the Republic of the Philippines, is an Archipelagic state, archipelagic country in Southeast Asia. Located in the western Pacific Ocean, it consists of List of islands of the Philippines, 7,641 islands, with a tot ...
, 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 New York, often called New York City (NYC), is the most populous city in the United States, located at the southern tip of New York State on one of the world's largest natural harbors. The city comprises five boroughs, each coextensive w ...
,
Texas Texas ( , ; or ) is the most populous U.S. state, state in the South Central United States, South Central region of the United States. It borders Louisiana to the east, Arkansas to the northeast, Oklahoma to the north, New Mexico to the we ...
, and
Mexico City Mexico City is the capital city, capital and List of cities in Mexico, largest city of Mexico, as well as the List of North American cities by population, most populous city in North America. It is one of the most important cultural and finan ...
, none of which produced cases of infection. By January 1990, Hazleton Laboratories recovered from its previous losses and began importing monkeys again from the same establishment in
Manila Manila, officially the City of Manila, is the Capital of the Philippines, capital and second-most populous city of the Philippines after Quezon City, with a population of 1,846,513 people in 2020. Located on the eastern shore of Manila Bay on ...
that had provided the original animals. The imported monkeys became infected and were euthanized. 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
import An importer is the receiving country in an export from the sending country. Importation and exportation are the defining financial transactions of international trade. Import is part of the International Trade which involves buying and receivin ...
ation of monkeys into the United States from anywhere in the world. 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 Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...
. 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 Sumatra () is one of the Sunda Islands of western Indonesia. It is the largest island that is fully within Indonesian territory, as well as the list of islands by area, sixth-largest island in the world at 482,286.55 km2 (182,812 mi. ...
. The investigation team found no trace of the virus in either case. Following the investigation in Indonesia, an experiment was conducted in the level-4 lab at the CDC campus in
DeKalb County DeKalb County may refer to one of several counties in the United States, all of which were named for Baron Johann de Kalb: * DeKalb County, Alabama DeKalb County is a County (United States), county in the Northeast Alabama, northeastern part ...
, Georgia with thirty-two monkeys: sixteen
green monkey The green monkey (''Chlorocebus sabaeus''), also known as the sabaeus monkey, is an Old World monkey with golden-green fur and pale hands and feet. The tip of the tail is golden yellow as are the backs of the thighs and cheek whiskers. It does n ...
s (''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 An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
.


Post-Reston

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 Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had ...
. One of the two monkeys remained resistant; the second died. The physical building in which the outbreak occurred was demolished on 30 May 1995 and a daycare center was constructed in its place. Modern spatial computer simulation indicates that the pathogen could have reached both major airports (
Dulles International Airport Washington Dulles International Airport ( ) – commonly known by its former name of Dulles International Airport, by its airport code of IAD, or simply as Dulles Airport – is an international airport in the Eastern United States, located w ...
and
Ronald Reagan Washington National Airport Ronald Reagan Washington National Airport is a public airport in Arlington County, Virginia, United States, from Washington, D.C. The closest airport to the nation's capital, it is one of two airports owned by the federal government and ope ...
) in less than 45 minutes assuming direct transmission paths.


Outbreaks and cases

* 1989 –1990 Philippines – High mortality among
crab-eating macaque The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settlem ...
s in a primate facility responsible for exporting animals in the United States. Three workers in the facility developed antibodies but did not get sick. * 1989 Reston, Virginia, United States – RESTV was introduced into quarantine facilities in Virginia and Pennsylvania by monkeys imported from the Philippines. * 1989–1990 – RESTV was introduced into quarantine facilities in Texas by monkeys imported from the Philippines. Four humans developed antibodies but did not get sick. * 1996 Alice, Texas, United States – An outbreak occurred at the Texas Primate Center that imported monkeys from the Philippines. * 2008 Manila, Philippines – On 11 December 2008, pigs from farms slightly north of
Manila Manila, officially the City of Manila, is the Capital of the Philippines, capital and second-most populous city of the Philippines after Quezon City, with a population of 1,846,513 people in 2020. Located on the eastern shore of Manila Bay on ...
,
Philippines The Philippines, officially the Republic of the Philippines, is an Archipelagic state, archipelagic country in Southeast Asia. Located in the western Pacific Ocean, it consists of List of islands of the Philippines, 7,641 islands, with a tot ...
tested positive for the virus. The
CDC The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
and the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
are investigating. On 23 January 2009, Philippine health officials announced that a hog farm worker had been infected with the virus. Although the man was asymptomatic and the source of the infection is uncertain, this could represent the first case of pig-to-human transmission of Reston virus – a fact that could cause concern, as pigs may be able to transmit more deadly diseases to humans. The situation was investigated. Eventually six workers were found to test sero-positive for antibodies to ''Reston ebolavirus''. None developed any noticeable symptoms of illness. * 2015 Manila, Philippines – On 6 September the department of health reported an outbreak of the Reston Ebola virus in a research breeding facility under primates. Twenty-five workers were tested for the virus. All of the workers tested negative for the disease.


In popular culture

*
Richard Preston Richard Preston (born August 5, 1954) is a writer for ''The New Yorker'' and bestselling author who has written books about infectious disease, bioterrorism, redwoods and other subjects, as well as fiction. Biography Preston was born in Cambr ...
's 1994 best-selling book, ''
The Hot Zone ''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 ...
'', dramatized the Ebola virus outbreak in Reston, Virginia.(1) At
Google Books Google Books (previously known as Google Book Search, Google Print, and by its code-name Project Ocean) is a service from Google that searches the full text of books and magazines that Google has scanned, converted to text using optical charac ...
.
(2)
(3)
In 2019
National Geographic ''National Geographic'' (formerly ''The National Geographic Magazine'', sometimes branded as ''Nat Geo'') is an American monthly magazine published by National Geographic Partners. The magazine was founded in 1888 as a scholarly journal, nine ...
aired a six-episode miniseries, also titled ''
The Hot Zone ''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 ...
''.


References


Bibliography

* * Preston, Richard (1997).
The Hot Zone ''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 ...
. Anchor Books (June 15, 1999). {{Authority control Animal viral diseases Arthropod-borne viral fevers and viral haemorrhagic fevers Biological agents Hemorrhagic fevers Ebolaviruses Tropical diseases Primate diseases Reston, Virginia Virus-related cutaneous conditions Zoonotic viral diseases