African swine fever virus


African swine fever virus is a large, double-stranded DNA virus in the Asfarviridae family. It is the causative agent of African swine fever. The virus causes a hemorrhagic fever with high mortality rates in domestic pigs; some isolates can cause death of animals as quickly as a week after infection. It persistently infects its natural hosts, warthogs, bushpigs, and soft ticks of the genus Ornithodoros, which likely act as a vector, with no disease signs. It does not cause disease in humans. ASFV is endemic to sub-Saharan Africa and exists in the wild through a cycle of infection between ticks and wild pigs, bushpigs, and warthogs. The disease was first described after European settlers brought pigs into areas endemic with ASFV, and as such, is an example of an emerging infectious disease.
ASFV replicates in the cytoplasm of infected cells. It is the only virus with a double-stranded DNA genome known to be transmitted by arthropods.

Virology

ASFV is a large, icosahedral, double-stranded DNA virus with a linear genome of 189 kilobases containing more than 180 genes. The number of genes differs slightly among different isolates of the virus. ASFV has similarities to the other large DNA viruses, e.g., poxvirus, iridovirus, and mimivirus. In common with other viral hemorrhagic fevers, the main target cells for replication are those of monocyte, macrophage lineage. Entry of the virus into the host cell is receptor-mediated, but the precise mechanism of endocytosis is presently unclear.
The virus encodes enzymes required for replication and transcription of its genome, including elements of a base excision repair system, structural proteins, and many proteins that are not essential for replication in cells, but instead have roles in virus survival and transmission in its hosts. Virus replication takes place in perinuclear factory areas. It is a highly orchestrated process with at least four stages of transcription—immediate-early, early, intermediate, and late. The majority of replication and assembly occurs in discrete, perinuclear regions of the cell called virus factories, and finally progeny virions are transported to the plasma membrane along microtubules where they bud out or are propelled away along actin projections to infect new cells. As the virus progresses through its lifecycle, most if not all of the host cell's organelles are modified, adapted, or in some cases destroyed.
cell in early stages of infection with ASFV
Assembly of the icosahedral capsid occurs on modified membranes from the endoplasmic reticulum. Products from proteolytically processed polyproteins form the core shell between the internal membrane and the nucleoprotein core. An additional outer membrane is gained as particles bud from the plasma membrane. The virus encodes proteins that inhibit signalling pathways in infected macrophages and thus modulate transcriptional activation of immune response genes. In addition, the virus encodes proteins which inhibit apoptosis of infected cells to facilitate production of progeny virions. Viral membrane proteins with similarity to cellular adhesion proteins modulate interaction of virus-infected cells and extracellular virions with host components.

Genotypes

Based on sequence variation in the C-terminal region of the B646L gene encoding the major capsid protein p72, 22 ASFV genotypes have been identified. All ASFV p72 genotypes have been circulating in eastern and southern Africa. Genotype I has been circulating in Europe, South America, the Caribbean, and western Africa. Genotype VIII is confined to four East African countries.

Evolution

The virus is thought to be derived from a virus of soft tick that infects wild swine, including giant forest hogs, warthogs, and bushpigs. In these wild hosts, infection is generally asymptomatic. This virus appears to have evolved around 1700 AD.
This date is corroborated by the historical record. Pigs were initially domesticated in North Africa and Eurasia. They were introduced into southern Africa from Europe and the Far East by the Portuguese and Chinese, respectively. At the end of the 19th century, the extensive pig industry in the native region of ASFV started after massive losses of cattle due to a rinderpest outbreak. Pigs were imported on a massive scale for breeding by colonizers from Seychelles in 1904 and from England in 1905. Pig farming was free-range at that time. The first outbreak of ASF was reported in 1907.

Taxonomy

ASFV is the only species in the order Asfuvirales, family Asfarviridae, and genus Asfivirus. Each of these three taxa is at least partly named after ASFV.

Signs and symptoms

In the acute form of the disease caused by highly virulent strains, pigs may develop a high fever, but show no other noticeable symptoms for the first few days. They then gradually lose their appetites and become depressed. In white-skinned pigs, the extremities turn blueish-purple and hemorrhages become apparent on the ears and abdomen. Groups of infected pigs lie huddled together shivering, breathing abnormally, and sometimes coughing. If forced to stand, they appear unsteady on their legs; this is called congenital tremor type A-I in newborn piglets. Within a few days of infection, they enter a comatose state and then die. In pregnant sows, spontaneous abortions occur.
In milder infections, affected pigs lose weight, become thin, and develop signs of pneumonia, skin ulcers, and swollen joints.

Diagnosis

The clinical symptoms of ASFV infection are very similar to classical swine fever, and the two diseases normally have to be distinguished by laboratory diagnosis. This diagnosis is usually performed by an ELISA or isolation of the virus from either the blood, lymph nodes, spleen, or serum of an infected pig.

Spread

The virus can be spread by ticks, but also by swine eating pork products that contain the virus.
The National Pig Association, a UK industry body, states that the virus can also be transmitted by direct or indirect contact with infected pigs, faeces or body fluids. As the virus may survive 11 days in pig faeces, and months or years in pork products, the association advises strict biosecurity measures for pig farms including a three-day quarantine on entering the UK, and avoiding both pigs and areas where wild boar are found.

Vaccine research

As of 2020, no vaccine is commercially available. Immunity appears to be largely strain specific. An experimental vaccine is in development against the 2007 Georgia isolate currently circulating, which is attenuated by deletion of the viral I177L gene.

History

The first outbreak was retrospectively recognized as having occurred in 1907 after ASF was first described in 1921 in Kenya. The disease remained restricted to Africa until 1957, when it was reported in Lisbon, Portugal. A further outbreak occurred in Portugal in 1960. Subsequent to these initial introductions, the disease became established in the Iberian peninsula, and sporadic outbreaks occurred in France, Belgium, and other European countries during the 1980s. Both Spain and Portugal had managed to eradicate the disease by the mid-1990s through a slaughter policy.
ASFV crossed the Atlantic Ocean, and outbreaks were reported in some Caribbean islands, including Hispaniola. Major outbreaks of ASF in Africa are regularly reported to the World Organisation for Animal Health.
In 2018 the virus spread to Asia, affecting more than 10 percent of the total pig population in several countries, leading to severe economic losses in the pig sector.

Cuba

In 1971, an outbreak of the disease occurred in Cuba, resulting in the slaughter of 500,000 pigs to prevent a nationwide animal epidemic. The outbreak was labeled the "most alarming event" of 1971 by the United Nations Food and Agricultural Organization.
Six years after the event, the newspaper Newsday, citing untraceable sources, claimed that anti-Castro saboteurs, with at least the tacit backing of U.S. Central Intelligence Agency officials, allegedly introduced African swine fever virus into Cuba six weeks before the outbreak in 1971, to destabilize the Cuban economy and encourage domestic opposition to Fidel Castro. The virus was allegedly delivered to the operatives from an army base in the Panama Canal Zone by an unnamed U.S. intelligence source.

Western Europe

ASFV first occurred in Europe in 1957, when it was introduced in Portugal. From there, it spread to Spain and France. Although concerted efforts to eradicate ASFV were undertaken, such as widespread culling and the construction of modern farming facilities, the disease was only eradicated in the 1990s.
In September 2018, an outbreak occurred in wild boars in southern Belgium. Professional observers suspect that importation of wild boars from Eastern European countries by game hunters was the origin of the virus. By the 4 October, 32 wild boars had tested positive for the virus. For control of the outbreak, 4,000 domestic pigs were slaughtered preventively in the Gaume region, and the forest was declared off-limits for recreation.

Eastern and Northern Europe

An outbreak occurred at the beginning of 2007 in Georgia, and subsequently spread to Armenia, Azerbaijan, Iran, Russia, and Belarus, raising concerns that ASFV may spread further geographically and have negative economic effects on the swine industry.
African swine fever had become endemic in the Russian Federation since spreading into the North Caucasus in November 2007, most likely through movements of infected wild boar from Georgia to Chechnya, said a 2013 report by the Food and Agriculture Organization, a United Nations agency. The report showed how the disease had spread north from the Caucasus to other parts of the country where pig production was more concentrated the Central Federal District and the Volga Federal District and northwest towards Ukraine, Belarus, Poland and the Baltic nations. In Russia, the report added, the disease was 'on its way to becoming endemic in Tver oblast' areas, travelling large distances within the country.
"Wholesale buyers, particularly the military food supply system, hav been implicated multiple times in the illegal distribution of contaminated meat" were vectors for the virus's spread, said the Food and Agriculture Organization report—and evidence of that was "repeated outbreaks in Leningrad oblast". The report warned that "countries immediately bordering the Russian Federation, particularly Ukraine, Moldova, Kazakhstan, and Latvia, are most vulnerable to introduction and endemic establishment, largely because the biosecurity of their pig sector is predominantly low. Preventing the spread of into Ukraine is particularly critical for the whole pig production sector in Europe. Given the worrisome developments in the Russian Federation, European countries have to be alert. They must be ready to prevent and to react effectively to introductions into their territories for many years to come...". To stop the virus's spread, "the current scenario in the Russian Federation suggests that should be particularly stressed at the often informal backyard level and should involve not just pig keepers, but all actors along the whole value chain—butchers, middlemen, slaughterhouses, etc. … They need to be aware of how to prevent and recognize the disease, and must understand the importance of reporting outbreaks to the national authorities … It is particularly important that -free areas remain free by preventing the introduction of the disease and by swiftly responding to it when it occurs".
Since around 2007 to August 31, 2018, 1367 cases of ASF of domestic pigs or wild pigs were reported by veterinary department of the Rosselkhoznadzor, a Russian federal agency that supervises over agriculture, and state media. According to official report the central and south districts were among most affected by the disease. Many regions effectively established local quarantines some of which was ended later.
In August 2012, an outbreak of African swine fever was reported in Ukraine.
In June 2013, an outbreak was reported in Belarus.
In January 2014, authorities announced the presence of African swine fever in Lithuania and Poland, in June 2014 in Latvia, and in July 2015 in Estonia.
Estonia in July 2015 recorded its first case of African swine fever in farmed pigs in Valgamaa on the country's border with Latvia. Another case was reported same day in Viljandi county, which also borders Latvia. All the pigs were culled and their carcasses incinerated. Less than a month later, almost 15,000 farmed pigs had been culled and the country was "struggling to get rid of hundreds of tons of carcasses". The death toll was "expected to rise".
Latvia in January 2017 declared African swine fever emergency in relation to outbreaks in three regions, including a pig farm in Krimulda region, that resulted in a cull of around 5,000 sows and piglets by using gas. In February, another massive pig cull was required, after an industrial-scale farm of the same company in Salaspils region was found infected, leading to a cull of about 10,000 pigs.
In June 2017, the Czech Republic recorded its historically first case of African swine fever. The veterinary administration of Zlin prevented the spread of the ASF infection by confining the contaminated zone via odor fences. Odor fences with a total length of 44.5 km were effective in keeping wild boar inside the health zone.
In 2018, Romania experienced a nation-wide African swine fever pandemic, which prompted the slaughter of most farm pigs.
In August 2018, authorities announced the first outbreak of African swine fever in Bulgaria. By July 2019 five Bulgarian pig farms had had outbreaks of African swine fever.
In July 2019, authorities announced the first outbreak of African swine fever in Slovakia.
In February 2020, authorities announced the first outbreak of African swine fever in a restricted area of Northern Greece.

Asia

; China
In August 2018, China reported the first African swine fever outbreak in Liaoning province, which was also the first reported case in East Asia. By September 1, 2018, the country had culled more than 38,000 hogs. Since the week of September 10, 2018, China has blocked transports of live pigs and pig products in a large part of the country to avoid spread beyond the 6 provinces where the virus was then confirmed. By the end of 2018, the outbreaks had been reported in 23 provinces and municipalities across China. On April 25, 2019, the virus was reported to have spread to every region of China, as well as parts of Southeast Asia, including Cambodia, Laos, Thailand and Vietnam. The Chinese pig population was reported to have declined by almost 40 million compared with the previous year.
Ze Chen, Shan Gao, and co-workers from Nankai University detected ASFV in Dermacentor from sheep and bovines using small RNA sequencing. This 235-bp segment had an identity of 99% to a 235-bp DNA segment of ASFV and contained three single nucleotide mutations. C38T, resulting in a single amino-acid mutation G66D, suggests the existence of a new ASFV strain, which is different from all reported ASFV strains in the NCBI GenBank database and the ASFV strain reported in China in 2018. In December 2019, China banned imports of pigs and wild boars from Indonesia because of African swine fever outbreaks that reached 392 in 17 December. On May 29, China’s Ministry of Agriculture and Rural Affairs said on Friday it had found a new outbreak of African swine fever near the city of Lanzhou in northwestern Gansu province.
; Philippines
The Philippines' Department of Agriculture started a probe in August 2019 regarding incidents of hog deaths in towns in Rizal and Bulacan for suspected African swine fever cases. The department ordered the culling of pigs within a radius of affected farms.
The first case of African swine fever in the Philippines was confirmed on 9 September 2019 by the country's agriculture department. The department sent 20 blood samples to the United Kingdom for testing, with 14 samples testing positive for African swine fever virus. At the time of the confirmation, though, the department has stated that the disease has not reached epidemic levels yet and is still assessing its severity.
On 16 September 2019, the Bureau of Animal Industry's Director Ronnie Domingo confirmed that the status of the virus in the country is in an outbreak level in Rizal, Bulacan, Quezon City, and also confirmed across the provinces of Pampanga and Pangasinan in the end of September.
; Vietnam
Vietnam confirmed its first case of African swine fever on 19 February 2019. As of 31 October 2019, all 63 provinces / municipalities have reported outbreaks and more than 5,700,000 pigs have been culled.
The Vietnamese government acted to limit movement of pigs and pig products and implemented measures to prevent, promptly detect and strictly handle cases of smuggling, illegal transportation, and trafficking of animals and animal products—especially of pigs and pig products—into the country.
; South Korea
On September, 2019, South Korea confirmed a second case of African swine fever at a pig farm in Yeoncheon, where 4,700 pigs had been raised, a day after reporting its first-ever outbreak of the virus. As of 31 October 2019, the virus has been detected in domestic pigs in nine places in Gyeonggi-do and five places in Incheon City. It was also confirmed in 18 wild boars from Gangwon-do and Gyeonggi-do, inside or near the Civilian Control Zone.
The South Korean government set a buffer zone to separate affected areas from the rest of the country and instituted a compensation scheme for farms within of infected farms.
; East Timor
ASF was reported on farms near the capital city, Dili in East Timor from 9 September 2019. On 30 September 2019, it was reported that 405 animals were killed or culled.
By the end of October 2019, a total of 100 outbreaks in smallholder pig farms had been recorded in Dili.
; India
On 29 April 2020, India reported the first African Swine Fever disease outbreak in the state of Assam and Arunachal Pradesh. It has been said that the disease is being spread via transboundary transmission from China. According to the data available with the veterinary department, over 15,000 pigs has been recorded dead from the 9 affected districts so far in Assam viz. Golaghat, Majuli, Dibrugarh, Kamrup, Dhemaji, Biswanath, North Lakhimpur, Sivasagar, Jorhat. Sale and consumption of pork meat have been banned in the affected districts of Assam. On 4 July, the test results of certain pig carcass samples came in as a confirmation for African Swine Fever in Bokakhat subdivision of Golaghat. The pig mortality reached around 800 numbers in Bokakhat. It is suspected that the infection came into the region from Kamargaon which is located near Bokakhat.
; Taiwan
Between December 2018 and June 2019, ten pig carcasses infected with ASF washed up on the shore in Kinmen county. In June 2019, the government temporarily halted export of pigs and pork products from Kinmen county after two infected pig carcasses were discovered on the shore. Nearby farms were inspected by veterinarians and no live pigs tested positive for ASF. On February 3, 2020, another infected pig carcass was discovered on the shore of Lieyu, bringing the total number of infected pig carcasses found on Kinmen county shores to eleven. In April 2020, a twelfth pig carcass confirmed to be carrying African swine fever virus washed up on the shore of Lieyu. After testing, no outbreak of the disease was detected in the seven active hog farms on the island.
On April 9, 2019, a pig carcass with ASF was discovered on the shore of Nangan in the Matsu Islands leading to a week-long ban on the transport of pigs from the county.

Historical theories

The appearance of ASF outside Africa at about the same time as the emergence of AIDS led to some interest in whether the two were related, and a report appeared in The Lancet supporting this in 1986. However, the realization that the human immunodeficiency virus causes AIDS discredited any potential connection with ASF.