Immunology and Infectious Disease Commons^™

Defective Transcriptional Programming Of Effector Cd8 T Cells In Aged Mice Is Cell-Extrinsic And Can Be Corrected By Administration Of Il-12 And Il-18, Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich

Peer Reviewed Articles

In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8 T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naïve CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naïve T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naïve adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by …

Influence Of Social Isolation During Prolonged Simulated Weightlessness By Hindlimb Unloading, Candice G.T. Tahimic, Amber M. Paul, Ann-Sofie Schreurs, Samantha M. Torres, Linda Rubinstein, Sonette Steczina

Publications

The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation …

Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla

School of Veterinary and Biomedical Sciences: Faculty Publications

Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause herediatry hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectase, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-B receptor complex and …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

The Skiles Mummy: Care Of A Debilitated Hunter-Gatherer Evidenced By Coprolite Studies And Stable Isotopic Analysis Of Hair, Kirsten A. Verostick, Isabel Teixeira-Santos, Vaughn M. Bryant Jr., Karl Reinhard

Karl Reinhard Publications

The Skiles Mummy (SMM), a naturally mummified adult male from the late archaic period of Lower Pecos Canyonlands of South Texas, represents a unique case of care. SMM is an exceptional mummy within this region due to both the retention of a full head of hair, and having a diagnosed case of megacolon, a complication commonly associated with Chagas disease caused by Trypanosoma cruzi. Stable isotopic analysis of his hair is consistent with a diet incorporating of C₄/CAM plants with some C₃ plants, freshwater resources, and higher trophic level animals. However, the segments of hair most …

Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).

Methods: Paired samples of clinical cases and unaffected controls …

The Nuclear 18s Ribosomal Dnas Of Avian Haemosporidian Parasites, Josef Harl, Tanja Himmel, Gediminas Valkiūnas, Herbert Weissenböck

Harold W. Manter Laboratory of Parasitology: Library Materials

Background: Plasmodium species feature only four to eight nuclear ribosomal units on different chromosomes, which are assumed to evolve independently according to a birth-and-death model, in which new variants originate by duplication and others are deleted throughout time. Moreover, distinct ribosomal units were shown to be expressed during different developmental stages in the vertebrate and mosquito hosts. Here, the 18S rDNA sequences of 32 species of avian haemosporidian parasites are reported and compared to those of simian and rodent Plasmodium species.

Methods: Almost the entire 18S rDNAs of avian haemosporidians belonging to the genera Plasmodium (7), Haemoproteus (9), …

Extracellular Vesicle-Mediated Macrophage Activation: An Insight Into The Mechanism Of Thioredoxin-Mediated Immune Activation, Chontida Yarana, Hannah Thompson, Luksana Chaiswing, D. Allan Butterfield, Heidi L. Weiss, Subbarao Bondada, Sara S. Alhakeem, Suriyan Sukati, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Extracellular vesicles (EVs) generated from redox active anticancer drugs are released into the extracellular environment. These EVs contain oxidized molecules and trigger inflammatory responses by macrophages. Using a mouse model of doxorubicin (DOX)-induced tissue injury, we previously found that the major sources of circulating EVs are from heart and liver, organs that are differentially affected by DOX. Here, we investigated the effects of EVs from cardiomyocytes and those from hepatocytes on macrophage activation. EVs from H9c2 rat cardiomyocytes (H9c2 EVs) and EVs from FL83b mouse hepatocytes (FL83 b EVs) have different levels of protein-bound 4-hydroxynonenal and thus different immunostimulatory effects …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

A Role Of Ubiquitin Regulatory X-Domain Containing Proteins (Ubxn6) In Antiviral Immunity, Harshada Ketkar, Harshada Ketkar

NYMC Student Theses and Dissertations

The roles of UBXNs in the regulation of antiviral immune responses have not been much explored. Previous work in our lab identified UBXN1 as a negative regulator of the retinoic acid-inducible gene-I (RIG-I) like receptors (RLR) pathway and UBXN3B as a positive regulator of stimulator-of-interferon Genes (STING) -mediated immune responses. In this study, I aimed to determine the member of UBXNs as a positive regulator of ribonucleic acid (RNA) virus infection-induced innate immune responses. By using an interferon stimulated response element (ISRE)-driven luciferase reporter assay that monitors the activity of type I/III interferon (IFN)-induced janus kinase (JAK) - signal transducer …

An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) And Non-Structural Protein 1 (Ns1) Confers Complete Protection Against Lethal Challenge In A Mouse Model, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Zack P. Guinn, Brianna L. Bullard, Eric A. Weaver, David J. Steffen, Sathish Kumar Natarajan, Thomas M. Petro, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine …

Il-17-Cxcr2 Axis Promotes Breast Cancer Metastasis And Therapy Resistance, Lingyun Wu

Theses & Dissertations

Cancer-related fatalities rank as the second leading cause of death in all ages and both genders in the United States. Moreover, breast cancer-related mortality rank as the second leading cause of death in females in the United States in 2019. The main concerns regarding breast cancer management include chemotherapy resistance and metastasis. Thus, the advanced understanding of cancer progression is required to develop improved therapeutic methods for breast cancer patients.

Recent studies demonstrate that neutrophils, as the most abundant leukocytes, play an essential role in breast progression. However, the mechanisms regarding neutrophils recruitment to the tumor sites, and the precise …

Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller

Publications and Research

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …

Synthesis And Evaluations Of “1,4-Triazolyl Combretacoumarins” And Desmethoxy Analogs, Tashrique A. Khandaker, Jessica D. Hess, Renato Aguilera, Graciela Andrei, Robert Snoeck, Dominique Schols, Padmanava Pradhan, Mahesh K. Lakshman

Publications and Research

1,4-Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3-triazole. For this, 4-azidocoumarins were accessed by a sequential two-step, one-pot reaction of 4-hydroxycoumarins with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN₃. In the reaction with BOP, a coumarin-derived phosphonium ion intermediate seems to form, leading to an O⁴-(benzotriazolyl)coumarin derivative. For the CuAAC reaction of azidocoumarins with 5-ethynyl-1,2,3-trimethoxybenzene, catalytic [(MeCN)₄Cu]PF₆ in CH₂Cl₂/MeOH with 2,6-lutidine, at 50 ^oC, was suitable. The 4-azidocoumarins were less reactive as compared to PhN₃ and …

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

Graduate Theses/Dissertations

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Environmental Sampling Techniques For Herd-Level Surveillance Of Bovine Viral Diarrhea Virus, Jaden Carlson

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Control of Bovine Viral Diarrhea Virus (BVDV) relies on resource-intensive individual animal sampling to detect and remove persistently infected (PI) cattle. Herd-level surveillance tools would be useful for herds with unknown BVDV status and for monitoring herds with BVDV-free status. The overall objective of this thesis is to explore the viability of BVDV surveillance at a herd-level using samples collected without handling individual animals. The first objective was to determine the feasibility of using stable flies as a sampling tool to detect BVDV. The second objective was to determine the feasibility of using drinking water to detect BVDV. To accomplish …

The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui

Electronic Theses and Dissertations

Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins α_Dβ₂ and α_Mβ₂ to macrophage migration and development of chronic inflammation.

We found that integrin α_Dβ₂ is upregulated on M1-macrophages in vitro and …

Bilirubin Nanoparticle As An Anti-Inflammatory Therapy For Graft Versus Host Disease, Sumedha Pareek

Dissertations and Theses (Open Access)

Graft versus host disease (GvHD) caused by alloreactive donor lymphocytes is a fatal complication of hematopoietic stem cell transplant (HSCT). Myeloablative conditioning regimen, consisting of chemotherapy and/or radiation, given prior to HSCT can cause tissue damage. This non-specific tissue damage triggers cross-presentation of alloantigens to the donor immune cells, causing recruitment of leukocytes and production of inflammatory cytokines. Targeting this inflammation without affecting the anti-leukemia effects of HSCT, continues to be one of the biggest challenge in finding a therapy for GvHD. Bilirubin is a tetrapyrrole pigment, found in the blood, with natural anti-oxidative and anti-inflammatory properties. Using mouse models …

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

Combating Tuberculosis: Using Time-Dependent Sensitivity Analysis To Develop Strategies For Treatment And Prevention, Kendall B. Clark, Mayleen Cortez, Cristian Hernandez, Beth E. Thomas, Allison L. Lewis

Spora: A Journal of Biomathematics

Although many organizations throughout the world have worked tirelessly to control tuberculosis (TB) epidemics, no country has yet been able to eradicate the disease completely. We present two compartmental models representing the spread of a TB epidemic through a population. The first is a general TB model; the second is an adaptation for regions in which HIV is prevalent, accounting for the effects of TB/HIV co-infection. Using active subspaces, we conduct time-dependent sensitivity analysis on both models to explore the significance of certain parameters with respect to the spread of TB. We use the results of this sensitivity analysis to …

Type X Strains Of Toxoplasma Gondii Are Virulent For Southern Sea Otters (Enhydra Lutris Nereis) And Present In Felids From Nearby Watersheds, Karen Shapiro, Elizabeth Vanwormer, Andrea Packham, Erin Dodd, Patricia A. Conrad, Melissa Miller

School of Veterinary and Biomedical Sciences: Faculty Publications

Why some Toxoplasma gondii-infected southern sea otters (Enhydra lutris nereis) develop fatal toxoplasmosis while others have incidental or mild chronic infections has long puzzled the scientific community. We assessed robust datasets on T. gondii molecular characterization in relation to detailed necropsy and histopathology results to evaluate whether parasite genotype influences pathological outcomes in sea otters that stranded along the central California coast. Genotypes isolated from sea otters were also compared with T. gondii strains circulating in felids from nearby coastal regions to assess land-to-sea parasite transmission. The predominant T. gondii genotypes isolated from 135 necropsied sea otters were atypical Type …

Role Of Host Cell Β-Catenin During Toxoplasma Gondii Infection, Cameron H. Ranken

Biology ETDs

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …

A High Throughput Assay For The Detection Of Stimulator Of Interferon Genes (Sting) Agonists, Michael J. Ingling

Graduate School of Biomedical Sciences Theses and Dissertations

The innate immune system includes a menagerie of different cell types, each with a different role in the process of monitoring the body for invaders and presenting gathered debris (antigen) to the adaptive immune system. Somatic cells have intracellular receptors for the same purpose. Cancer cells, however, have avoided these methods of detection despite, in many cases, the tumor’s immunogenic traits. Immuno-oncology is a field dedicated to the immunological traits of tumors, more recently finding ways of instigating an immune response against tumors. In this regard, STING, a receptor of cyclic dinucleotides (CDN), has come to the forefront of immuno-oncology. …

Development Of A Prolyl Endopeptidase Expression System In Lactobacillus Reuteri To Reduce The Clinical Manifestation Of Celiac Disease, Kara Lynn Jew

Master's Theses

Celiac Disease (CD) is an autoimmune disorder that emerges due to the ingestion of gluten, a protein found in a variety of common grains such as wheat, rye, and barley. Approximately 1 in 100 individuals in the US suffer from CD, making it the most commonly diagnosed gastrointestinal disorder (Ciclitira et. al., 2005). These proline-rich gluten peptides are resistant to proteolysis and accumulate in the duodenum of the small intestine. Once in the duodenum, these peptides illicit an autoimmune response resulting in villous atrophy. Current treatment for CD requires a rigorous adherence to a gluten-free diet. Nevertheless, gluten-containing grains are …

The Wet Bridge Transfer System: An Novel In Vitro Tool For Assessing Exogenous Surfactant As A Pulmonary Drug Delivery Vehicle, Brandon J. Baer

Western Research Forum

Background:

Due to its complex branching structure, direct drug delivery to the remote areas of the lung is a major challenge. Consequently, most therapies, such as those treating pulmonary infection and inflammation, must utilize large systemic dosing, with the potential for adverse side effects. A novel alternative strategy is to use exogenous surfactant, a material capable of distributing throughout the lung, as a pulmonary drug delivery vehicle.

Objective:

Utilize an in vitro transferring system to assess exogenous surfactant (BLES) as a pulmonary delivery vehicle for different therapeutics.

Methods:

An in vitro technique was developed to simultaneously study surfactant delivery and …

Cell-Free Dna Release During Programmed Cell Death In Ischemia Reperfusion Injury, Alexander Dionne, Anthony M. Jevnikar, Zhu-Xu Zhang

Western Research Forum

Transplantation is invariably associated with acute allograft injury caused by ischemia reperfusion injury (IRI). This injury causes cells of the allograft to undergo various forms of programmed cell death including apoptosis and necroptosis. During programmed cell death, immunogenic molecules are released from cells, one of which is cell-free DNA (cfDNA). We hypothesize that cfDNA is released by microvascular endothelial cells (MVECs) during programmed cell death of IRI and that cfDNA acts as both a biomarker for cellular injury as well as a biologically active molecule capable of amplifying inflammation and organ injury.

Our results indicate that cfDNA is released by …

Cross-Species Genome-Wide Analysis Reveals Molecular And Functional Diversity Of The Unconventional Interferon-Ω Subtype, Lauren E. Shields, Jordan Jennings, Qinfang Liu, Jinhwa Lee, Wenjun Ma, Frank Blecha, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes …

Open Textbook Project [Poster], Sue Ann Gardner

University of Nebraska-Lincoln Libraries: Presentations

Details of a porject undertaken to collaboratively write and produce an open access parasitology textbook for undergraduate and graduate students. The book will be published by Zea Books at the University of Nebraska-Lincoln in 2020 and be available in English and Spanish both online and print-on-demand through lulu.com.

Co-Executive Editors: Scott L. Gardner and Sue Ann Gardner, University of Nebraska-Lincoln. Publisher: Paul Royster/Zea Books, University of Nebraska-Lincoln. Spanish Translator: Yoanna Esquivel Greenwood, University of Nebraska-Lincoln. Project Coordinator: Sue Ann Gardner.

Project website: Concepts in Animal Parasitology.

Porcine Interferon Complex And Co-Evolution With Increasing Viral Pressure After Domestication, Jordan Jennings, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and …