OSU researchers aim to find cure for PEDV, bovine herpesvirus 1

USDA NIFA grant to also fund research in forages, probiotics, alternative antibiotics, animal genomes and prenatal stress on pig microbiomes.

July 19, 2023

11 Min Read
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The USDA National Institute of Food and Agriculture has awarded a combined $4 million in grant funds to support the following Oklahoma State University Ag Research projects in animal and veterinary sciences.

Creating efficient forage users
David Lalman, OSU professor and Extension specialist for beef cattle and Harrington Endowed Chair, and his team are focused on finding cows that are efficient at using forage, which reduces the cost and carbon footprint of beef production.

The researchers will determine the most effective stage of production for identifying animals that are efficient forage users by looking at how much hay (forage) the animals consume, how much weight they gain or lose, and how much methane and carbon dioxide they produce.

"Beef cattle are unique in that they have the ability to convert sunlight, water and carbon dioxide into a high-quality human protein source through forages," Lalman said. "Our goal is to find animals that are highly efficient at converting forage to beef."

Researchers will test cows at the replacement heifer period (after weaning), during pregnancy when the cows are 4 years old and after they calve as 5-year-olds (while nursing their third calf). Researchers plan to use data to develop a prediction model that can rank cows from most to least efficient without having to perform a feed intake test.

Initial data suggested that the most efficient one-third of animals within each group consume about 22% less forage and produce about 11% less methane than the inefficient one-third of animals in that same group. That is a difference of about $121 per year per cow in production costs, which amounts to $3.75 billion per year in industrywide savings in the U.S. in feed costs at the cow/calf level.

"This work could lead to a practical method to identify cows that have the ability to efficiently produce weaned calves with minimal supplemental feed inputs that require less grazing land and have a smaller carbon footprint," Lalman said. 

Probiotics as an animal growth tool
Peter Muriana, research professor and Extension specialist for food microbiology, and his team are studying using probiotics in swine feed as a substitute for growth promotants.

"This research addresses the enhancement of animal growth using probiotic bacteria as an alternative to the overuse of growth promotants, including antibiotics, which would increase the safety of derived meat products," Muriana said.

Using low levels of antibiotics in animal feed increases animal growth by suppressing the animal's normal microorganisms. This enhances the animal’s nutrient use and suppresses gastrointestinal inflammation from a bacterial infection that would result in higher animal maintenance costs. However, using antibiotics in feed can also enrich antibiotic-resistant bacteria in an animal's intestines. This includes foodborne pathogens, which could contaminate harvested meat products and cause illness to humans if consumed in undercooked meats or through cross-contamination.

"If pathogenic bacteria in these animals are resistant to the same antibiotics given for human illness and humans consume contaminated meat products, then treatment of those humans with the same antibiotics might be ineffective, prolonging illness and even allowing illness to get worse," Muriana said. "Numerous pathogens harbor multiple drug resistance genes, so even giving animals antibiotics that are different than those given to humans may still have the same result."

Muriana said his team will screen for bacteria that are useful in helping swine digest complex components in animal feed. They will then place bacteria back into the animal's diet at levels higher than would normally occur on their own and boost them by providing prebiotic growth supplements for those bacteria.

This could provide more efficient use of nutrients in animal feed and result in weight gain to achieve the same results as traditional growth promotants.

"This could provide animal producers with a safe and effective alternative in swine," Muriana said. "If successful, it could serve as a model that could be replicated with other food production animals, such as beef."

Studying genome differences
Darren Hagen, assistant professor in animal and food sciences, and his team will work to better understand differences in the structure and interactions of animal genomes to benefit future research.

A genome is the complete set of genes or genetic material present in a cell or organism. Hagen's goal is to identify what genetics directly cause differences in economically important traits, such as how much milk a cow produces, weight, height and other measurable traits.

"One to 3% of the genome is genes that will be made into protein, while the other 97 to 99% we're generally clueless about," Hagen said. "We're trying to understand the three-dimensional structure of the genome and how different regions of the genome interact with each other because of the shape of that structure."

Hagen said if a chromosome moves in a particular way, then two points on the same chromosome could be far apart from one another but still interact with each other. These points could regulate how a gene is expressed.

Animals inherit different genetic patterns from their mother and father, and because those patterns are different, genes are expressed differently from maternal versus paternal chromosomes, Hagen said, highlighting that the following are factors with genetics:

  • Which parent gave the DNA could impact the three-dimensional shape of the genome.

  • The three-dimensional shape of the genome will impact how its genes are expressed.

  • How those genes are expressed will impact how the animal looks and behaves.

"So, the chromosomes from your mother may fold and interact differently than the chromosomes you got from your father," he said. "We are also trying to figure out how those unique patterns might dictate the three-dimensional shape for each of the parents' chromosomes. We can figure out which parent is which and what the differences in their genomes are. The father's genome folds this way, and the mother's folds that way."

To determine which genome belongs to which parent, researchers are creating bison/cow hybrids at the molecular level. Hagen said the genomes of males and females of the same species are more than 99% similar, so it is difficult to determine what traits came from which parent.

"When we make these hybrids, they're genetically different enough that we can start to see the individual genetics of each parent and how it has contributed to that animal's genome," he said.

When scientists sequence something, they cut it up into millions of pieces and throw it in a big pile, Hagen said.

"When I grab a piece out of the pile, and there is no difference between that piece and the last piece, that doesn't tell me any information," he said. "If it's DNA from cows and bison, then each time I grab something, there's a higher chance there is going to be a difference in the information."

Prenatal stress on pig microbiomes
Janeen Salak-Johnson, associate professor of animal and food sciences, and her research team will identify how microorganisms in the gut of stressed mother pigs impact unborn piglets.

The stress of a mother pig during pregnancy can affect the physiological and behavioral traits of her offspring before and after birth. This could contribute to long-term health and welfare problems later in life. Gut microorganisms influence physiological and health traits, such as brain development and the immune system, which can affect the behavior and well-being of an individual. Despite this, the measures of gut health are often absent from welfare assessments.

"Limited data exists on the effects of prenatal stress on the maternal gut microorganisms responsible for influencing the health and welfare of infant pigs," Salak-Johnson said. "Investigating the effects of maternal stress on the gut-brain-immune axis provides a novel approach to measuring animal welfare in both the short and long term. Data obtained from this study can be used to assess and improve poor animal welfare."

Salak-Johnson's research has the following goals:

  • Identify the role of gut microbes and immune responses in stressed mothers on the health and well-being of their offspring.

  • Characterize the effects of multiple stressors on the gut microbes on brain development and immune responses in offspring born to stressed sows.

  • Decipher the molecular gut microorganism signatures, gut-immune responses, and behavioral characteristics imprinted on the offspring in later generations.

"Our long-term goals are to describe the cross-talk between the resident microbiomes (gut, vagina and putative placenta) and hormones of stressed versus non-stressed pregnant pigs to define the microbiome, immune and behavioral imprinting of the offspring," Salak Johnson said. "We want to develop new intervention strategies to improve health and wellbeing across generations while promoting positive animal welfare and safeguarding animal agriculture."

Antibiotic alternatives for livestock diseases
In 2017, the U.S. Food and Drug Administration implemented plans to phase out the use of antibiotics in livestock industries because the drugs can be passed along to people, causing a rise in pathogens resistant to antibiotics. This has left these industries with the need to find an alternative way of reducing animal diseases, such as necrotic enteritis, which causes severe intestinal lesions, growth retardation and billions of dollars of loss to the poultry industry annually.

Through screening thousands of small, molecular compounds, Glenn Zhang, OSU Regents Professor and Boulware Endowed Chair of animal and food sciences, discovered several classes of epigenetic compounds that contribute to enhancing host defense and resistance to necrotic enteritis.

"These discoveries provided a timely opportunity to investigate the potential of these compounds as novel antibiotic alternatives," Zhang said. "The long-term goal of our research is to develop immune-boosting compounds as next-generation antibiotic alternatives for livestock use." 

Zhang said this latest research grant is aimed at further screening for the best combinations of epigenetic compounds to enhance disease resistance while also revealing the mechanism that causes this action. Epigenetic compounds refers tothose compounds that alter gene activities and visible genetic traits (phenotypes) without changing the genetic code.

"We expect to identify several combinations of epigenetic compounds that will be highly effective in disease alleviation," he said. 

Outcomes of the research will lead to the development of small molecule epigenetic compounds as the first-of-its-kind class of antibiotic alternatives for disease control and prevention in poultry and possibly other livestock species.

Finding a cure for a costly pig disease
Porcine epidemic diarrhea virus is a lethal coronavirus for newborn pigs and is a large threat to the U.S. pork industry. It resulted in a $1.8 billion loss to the industry from 2013 to 2014. PEDV continues to circulate in the U.S. with an average of 10-15% of pigs testing positive each year.

"An effective vaccine is not available to pork producers," said Xufang Deng, OSU assistant professor of physiological sciences in the College of Veterinary Medicine. "Current commercially available PEDV vaccines provide limited protection due to the inability of these vaccines to stimulate high-level protective antibodies in the milk (called lactogenic immunity) provided to piglets by sows."

The goal of Deng's research project is to develop oral PEDV live vaccine candidates that are safe and can provoke robust lactogenic immunity in sows, which is the sow's ability to produce proteins acting as antibodies in the milk they produce.

"Our earlier research discovered a handful of protein molecules encoded by the genetic materials of PEDV that are crucial for the virus counteracting the pig's immune system," Deng said.

These molecules, called immune antagonists, are key factors for the virus and could be genetically inactivated to develop vaccines that could bring out strong immune responses.

Deng's research team will use reverse genetic engineering technology to identify key immune antagonists that contribute to PEDV. They will generate PEDV mutants that have genetic mutations with minimal pathogenic qualities but produce strong antibody responses in newborn pigs. They will then evaluate candidates for creating a vaccine from the PEDV mutants in growing pigs.

"We anticipate these PEDV mutants will be safe oral vaccine candidates that can provide robust protection," Deng said. "The successful implementation of this study will not only aid pork producers in PEDV control and prevention but also provide veterinary researchers and vaccine manufacturers with a generalized approach for developing vaccines against other pig intestinal coronaviruses."

Curing respiratory disease in cattle
Bovine herpesvirus 1 is a major cattle pathogen that causes bovine respiratory disease, which results in economic losses exceeding $5 billion across the world each year. Additionally, BoHV-1 causes abortion in infected cows, causing major losses in breeding and the dairy industry.

The primary difficulty in controlling BoHV-1 infection is its lifecycle, said Jeff Ostler, assistant professor of veterinary pathobiology. The virus establishes a lifelong dormant infection in sensory neurons, making the virus nearly impossible to cure.

"This dormancy is marked by periodic reactivation, leading to acute disease symptoms, including respiratory disease and reproductive failure," Ostler said, adding that the virus is contagious, and stress can cause the virus to reactivate, particularly during transport. As a result, infected cows are more likely to spread BoHV-1 at the time they are in contact with other cows.

"There are two commercial vaccines, but they have not eliminated the virus, and in some cases, they have increased abortion rates in cows," Ostler said. "Our goal is to reduce the spread of BoHV-1 by blocking reactivation, much like how many human herpesviruses are controlled."

Since stress is a major driver of reactivation, Ostler said his research team has identified several key proteins that increase the BoHV-1 infection and reactivation.

Key among these is the glucocorticoid receptor, a protein expressed in most cells that drives the cellular stress response in reaction to specific hormones called corticosteroids.

"We are dissecting the mechanisms that BoHV-1 uses to hijack GR into driving its own gene expression toward productive infection," Ostler said. "From there, we are trying to block reactivation of the infection to decrease BoHV-1 spread."

The project will identify how GR controls BoHV-1 gene expression and what virus proteins are expressed early during reactivation.

"We must know these key steps to develop therapeutics targeting reactivation," Ostler said. "If we can effectively reduce BoHV-1 reactivation in infected cows, we can drastically reduce virus spread, which will lead to improved health outcomes in cattle, reduce economic losses and increase industry stability."

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