ARS working to protect domestic livestock from foreign disease outbreaks

A deadly animal virus is on the loose, treading through Russia and knocking on the doors of Eastern Europe and Asia. After its introduction into the Republic of Georgia and the Caucasus region in 2007 and spread into Russia, the virus that causes African swine fever (ASF) was spotted for the first time last year in Ukraine, putting European and Asian countries on high alert. The virus moves quickly, killing 100% of infected pigs within a week in some instances.

Standing between a possible U.S. invasion by foreign animal diseases like ASF is the Plum Island Animal Disease Center, situated off the northeastern tip of Long Island, New York. For almost 60 years, the center has served as somewhat of a fortress, where a small force of scientists tackles dangerous diseases that threaten the health of livestock and world economies.

In 1954, the U.S. Department of Agriculture’s Agricultural Research Service took over Plum Island from the U.S. Army to establish laboratories where scientists could find ways to prevent and control exotic diseases that threaten U.S. livestock production and global food security. The primary objective was to develop methods to detect and prevent foot-and-mouth disease (FMD), an economically devastating disease. FMD was eradicated from the United States in 1929, but today it is spreading throughout Asia and Africa. Recent outbreaks have occurred in the United Kingdom, Bulgaria, Japan, and South Korea.

Working with other agencies, scientists in the ARS Foreign Animal Disease Research Unit (FADRU), at Plum Island, also keep diseases like ASF, classical swine fever, and vesicular stomatitis at bay. In 1984, a USDA Animal and Plant Health Inspection Service (APHIS) team took over diagnostic work, leaving the basic research to ARS scientists. Another change occurred in 2003, when Plum Island operations were transferred to the U.S. Department of Homeland Security (DHS), which works with USDA in the advanced development of vaccines and diagnostic tests to help control and respond to disease outbreaks.

 

Tracking FMD: The infection site

The Plum Island center provides a safe setting for studying FMD, which affects cloven-hoofed animals like cattle, swine, sheep, goats, and deer. The highly contagious disease is rarely fatal in adult animals, but it debilitates its victims and can cause large-scale death of young animals. Incursions of FMD cause profound economic consequences through isolation from trade, loss in milk production, severe lameness, and massive depopulations. When the virus has been introduced in FMD-virus-free countries, millions of animals—infected and uninfected—have been euthanized after outbreaks to prevent the virus from spreading.

A breakthrough in FMD research came in 2010 when veterinary medical officer Jonathan Arzt identified the site where FMD virus initiates infection in cattle. Working with FADRU research leader Luis Rodriguez and microbiologist Juan Pacheco, Arzt found that the virus selectively infects epithelial cells in the back of the cow’s throat.

“Now that we’ve determined the actual route the virus takes in infected cattle, we can try to develop new vaccines and biotherapeutics to target and prevent virus infection of the primary site and potentially control and eradicate FMD,” Arzt said. “Blocking the initial site of infection is the best way to achieve complete protection.”

There are seven FMD virus serotypes—O, A, C, Asia-1, SAT-1, SAT-2, and SAT-3. Scientists detected the infection site using serotype O and have since had the same success with serotype A.

“The work with serotype A elevates our level of confidence even higher,” Arzt said. “We now know that what we found with serotype O was not an anomaly or isolated finding.”

In other work, scientists have helped build an infrastructure for testing, biosecurity measures, and identification of FMD virus strains in Vietnam and Pakistan. “Our goal is to help them discover how FMD outbreaks are initiated under natural conditions so they can protect their own herds, but it also gives us an advance look at the FMD virus strains that are currently emerging and circulating,” Arzt said.

In the last 15 years, FADRU scientists have proven that interferons—proteins made and released by host cells in response to the presence of viruses or other pathogens—protect against FMD. Interferons act as antiviral agents that kill the virus or stop it from multiplying and reproducing.

These vaccines require 7 days to induce protection against FMD, leaving vaccinated animals susceptible to infection during that time. Therefore, scientists are trying to cover that window of susceptibility by combining interferons with vaccines. Research into improving the delivery and production safety of the vaccines is ongoing.

 

A classic case of pig virus

Although classical swine fever (CSF) has been eradicated in the United States, the contagious, sometimes fatal disease is present in wildlife in Europe, where infected wild boar can transmit it to domestic pigs.

“Once the disease is detected, all animals in close proximity of infected pigs must be destroyed, creating a huge economic problem,” said microbiologist Manuel Borca. “Vaccination is banned in Europe, but it would be considered if a marker vaccine is developed.” A marker vaccine allows vaccinated animals to be distinguished from those infected with wild-type virus.

Under the leadership of Borca, scientists at Plum Island have been using different strategies to develop virus strains for vaccines that meet these criteria. They identified 10 to 12 different areas of the virus genome that, if mutated, cause the virus to become attenuated.

Using this approach, a CSF virus was genetically manipulated not only to attenuate it, but also to introduce a genetic marker that can distinguish it from wild-type virus. Borca received a patent for this marker virus, which produces early immunity within the first week of vaccination.

Earlier CSF work at Plum Island included the development of a rapid diagnostic test, based on real-time PCR (polymerase chain reaction), which detects the virus in infected animals 2 to 4 days before clinical signs appear. “The test was further validated using field samples in the Dominican Republic,” Borca said. “We showed that it works in field conditions.”

 

Combating African swine fever

An outbreak of African swine fever (ASF) in the Republic of Georgia and surrounding countries in 2007 prompted ARS to renew efforts to find ways to prevent or control this serious disease, for which there is no cure or vaccine. Concern over ASF is heightened by its unrelenting spread towards Europe since 2007. Its clinical signs are similar to those of CSF, but ASF is more uniformly fatal. Pigs suffer from high fever, hemorrhages, vomiting, and loss of appetite.

“African swine fever has many strains that are extremely infectious,” Borca said. “All infected animals die within a week.”

All attempts to produce effective vaccines have been unsuccessful so far because of the complexity and large size of the ASF virus.

“It has a large genome of more than 150 genes, making everything more complicated,” Borca said. “It is more difficult to research the ASF virus than the smaller viruses, like CSF.”

In earlier years, scientists at Plum Island made significant progress in understanding the role of particular ASF virus genes in causing disease. Borca was part of a team that was able to characterize several genes that are important in virulence.

“If you eliminated some of those genes, the virus became somewhat attenuated,” Borca said. “This approach was used at that time to develop less-virulent viruses that could be tested as vaccine candidates.”

Animals given the attenuated viruses and later challenged with a virulent virus were protected against ASF, he said.

After a 7-year lapse in ASF studies due to limited funding, research has been reinitiated by ARS scientists, under Borca’s leadership, using these same techniques.

“In the last 2 years, we have produced recombinant viruses, using the ASF strain that is killing thousands of animals in the Caucasus region, by eliminating the genes previously identified as important for attenuating the virus,” Borca said. “We are now testing those viruses in animals to see if they are attenuated and if they could be used as vaccine candidates.”

 

A blistering battle

Another livestock invader is vesicular stomatitis virus (VSV), which rarely occurs in the United States but can infect humans and some wildlife species.

“It looks like foot-and-mouth disease — blisters on the tongue, mouth, and fleshy parts of the feet,” Rodriguez said. “However, VSV affects horses, and FMD does not.”

No effective vaccines are available for the disease, and the virus is transmitted by insects. “Black flies and sand flies are involved, as are the tiny culicoides insects, also called ‘no-see-ems,’” Rodriguez said.

Working with scientists in Mexico, Rodriguez recently traced the origin of a large number of 2008 outbreaks in northern Mexico to southern Mexico. He identified the virus strain and predicted that it might spread to the United States. Indeed, this virus was the cause of outbreaks in New Mexico in 2012.

“We discovered that the virus that occurred in the United States actually comes from Mexico, but we don’t know how it gets here,” he said. “We think it’s by insects and have found that if we protect animals from bug bites, we can decrease the impact of the outbreak.”

 

Teamwork is key to success

While ARS scientists at Plum Island work with universities, industries, international organizations, and governments, their innovative technologies and discoveries are enhanced by APHIS and DHS support. The main goal is to prevent and control foreign animal diseases by developing improved tools for diagnosing diseases and creating safe, faster acting vaccines and biotherapeutics. APHIS confirms diagnostic tests and technologies for surveillance, detection, and response to disease threats. DHS assists in developing vaccines and other countermeasures required for an effective response to a foreign-animal-disease outbreak on U.S. soil. This diligent teamwork at Plum Island helps protect livestock, humans, and food supplies from diseases that put America at risk.

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