Maureen Kerrigan - Academia.edu (original) (raw)

Papers by Maureen Kerrigan

BMC Genomics, 2017

Background: The WUR1000125 (WUR) single nucleotide polymorphism (SNP) can be used as a genetic ma... more Background: The WUR1000125 (WUR) single nucleotide polymorphism (SNP) can be used as a genetic marker for host response to porcine reproductive and respiratory syndrome (PRRS), PRRS vaccination, and co-infection with porcine circovirus type 2b (PCV2b). Objectives of this study were to identify genomic regions other than WUR associated with host response to PRRS vaccination and PRRSV/PCV2b co-infection and regions with a different effect on host response to co-infection, depending on previous vaccination for PRRS. Methods: Commercial crossbred nursery pigs were pre-selected for WUR genotype (n = 171 AA and 198 AB pigs) where B is the dominant and favorable allele. Half of the pigs were vaccinated for PRRS and 4 weeks later, all pigs were co-infected with PRRS virus and PCV2b. Average daily gain (ADG) and viral load (VL) were quantified post vaccination (Post Vx) and post co-infection (Post Co-X). Single-SNP genome-wide association analyses were then conducted to identify genomic regions associated with response to vaccination and co-infection. Results: Multiple SNPs near the major histocompatibility complex were significantly associated with PCV2b VL (−log 10 P ≥ 5.5), regardless of prior vaccination for PRRS. Several SNPs were also significantly associated with ADG Post Vx and Post Co-X. SNPs with a different effect on ADG, depending on prior vaccination for PRRS, were identified Post Vx (−log 10 P = 5.6) and Post Co-X (−log 10 P = 5.5). No SNPs were significantly associated with vaccination VL (−log 10 P ≤ 4.7) or PRRS VL (−log 10 P ≤ 4.3). Genes near SNPs associated with vaccination VL, PRRS VL, and PCV2b VL were enriched (P ≤ 0. 01) for immune-related pathways and genes near SNPs associated with ADG were enriched for metabolism pathways (P ≤ 0.04). SNPs associated with vaccination VL, PRRS VL, and PCV2b VL showed overrepresentation of health QTL identified in previous studies and SNPs associated with ADG Post Vx of Non-Vx pigs showed overrepresentation of growth QTL. Conclusions: Multiple genomic regions were associated with PCV2b VL and ADG Post Vx and Post Co-X. Different SNPs were associated with ADG, depending on previous vaccination for PRRS. Results of functional annotation analyses and novel approaches of using previously-reported QTL support the identified regions.

Eighteen 8-week-old disease-free pigs were infected with Actinobacillus pleuropneumoniae (APP) se... more Eighteen 8-week-old disease-free pigs were infected with Actinobacillus pleuropneumoniae (APP) serotype 1 by in- tranasal inoculation. Serum antibody responses of 15 of these pigs to APP were measured before the trial and at 2, 4, 6, 9, 10, 12, 14, and 17 weeks post infection (PI) by antibody isotype-spe- cific ELISA (IgG, IgM, and IgA), complement fixation test (CF), and an Apx1 hemolysin neutralization (HN) test. All pigs were sero- logically negative by all tests prior to being exposed to APP. ELISA IgG, IgA, and HN titers increased by 2 weeks PI and remained stable throughout the sampling period. ELISA IgM titers peaked 2 weeks PI, declined gradually up to week 12, and again in- creased during the last 5 weeks of the experimental period. The CF titers were erratic with some pigs remaining negative throughout the study. Others were positive soon after becoming infected only to turn negative at later sampling times. Only one pig was CF positive at all sampling times PI.

Journal of Bacteriology

Nucleotide changes in the nifH gene of Klebsiella pneumoniae were identified by DNA cloning and s... more Nucleotide changes in the nifH gene of Klebsiella pneumoniae were identified by DNA cloning and sequencing of six selected mutant strains. The strains were UN60, C-640-GC----TGC; UN116, C-67-TC----TTC; UN117, G-688-AG----AAG; UN1041, CG-302-C----CAC; UN1678, GC-713-C----GTC; and UN1795, G-439-AG----AAG. Their corresponding amino acid substitutions were UN60, Arg-214----Cys; UN116, Leu-23----Phe; UN117, Glu-230----Lys; UN1041, Arg-101----His; UN1678, Ala-238----Val; and UN1795, Glu-147----Lys. Results from Western and Northern blots of the mutant strains showed significant reductions in both steady-state levels of the accumulated Fe protein and nifH mRNA during derepression in the presence of serine. The relative specific activities of the nitrogenases in strains UN60, UN1041, and UN1795 were less than 2% of the wild type, whereas those in UN116, UN117, and UN1678 were between 28 and 40% of the wild type during enhanced derepression with serine. The residues of Arg-101 (UN1041), Glu-...

The Biochemical journal, 1988

On the basis of the amino acid sequence of bovine rhodopsin, a series of peptides from the C-term... more On the basis of the amino acid sequence of bovine rhodopsin, a series of peptides from the C-terminus (Rhod-4 and Rhod-1) and external loops (Rhod-10) were synthesized. Rabbit antisera to these peptides recognize the rhodopsin molecule in whole retina from 8-week-old normal and affected rcdl (rod/cone-dysplasic) Irish setters (8- and 4-weeks-old). When the rhodopsin content was equalized by using a solid-phase radioimmunoassay, the reaction with anti-peptide antisera to the C-terminal octapeptide (residues 341-348) is severely decreased in the rcdl-dog retinas. The results of mixing experiments suggest that this is not due to proteolytic clipping of the rhodopsin C-terminus from the affected dogs. Treatment of retinas with 1.0 mM-NaF, a phosphatase inhibitor, or pretreatment with alkaline and acid phosphatases does alter the reaction of the rhodopsin with anti-rhodopsin antisera. This suggests that the decreased reaction of the affected rhodopsin with the anti-peptide antisera may p...

Biochemical and Biophysical Research Communications, 1988

The S-antigen (alias 48K protein or arrestin) of bovine rod photoreceptors contains two stretches... more The S-antigen (alias 48K protein or arrestin) of bovine rod photoreceptors contains two stretches of amino acid sequence homologous to the ADP-ribosylation sites of the alpha subunit of transducin (Ta). We have found that cholera toxin transfers the ADP-ribosyl group from NAD to purified bovine S-antigen as well as to Santigen in rod outer segment membranes, while Bordetella pertussis toxin is unable to catalize the transfer reaction efficiently. Under the same conditions, both toxins catalyzed ADP-ribosylation of Ta in rod outer segments. The ADP-ribosylation of S-antigen by cholera toxin indicates that S-antigen not only exhibits sequence homology with the ADP-ribosylation sites of Ta, but it must also resemble Ta in the tertiary structure of the domain which determines the susceptibility of S-antigen to the catalytic action of cholera toxin. These results suggest that S-antigen may function as a competitor of Ta in some stage of the cGMP cascade of visual transdnction.

Animal Industry Report, 2015

Average daily gain (ADG) and viral load (VL) were evaluated for pigs co-infected with porcine rep... more Average daily gain (ADG) and viral load (VL) were evaluated for pigs co-infected with porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) and porcine circovirus type 2b (PCV2b). Pigs were pre-selected for WUR genotype (a marker on chromosome 4 associated with weight gain and VL under PRRSV-challenge), half were vaccinated for PRRS, and half were not. Results indicate that vaccination for PRRS resulted in slower growth prior to co-infection and that the AB WUR genotype was associated with faster growth prior to co-infection, lower PRRS VL, and lower PCV2b VL in vaccinated pigs.

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, Jan 4, 2016

Genetic variation in both structural and nonstructural genes is a key factor in the capacity of p... more Genetic variation in both structural and nonstructural genes is a key factor in the capacity of porcine reproductive and respiratory syndrome virus (PRRSV) to evade host defenses and maintain within animals, farms and metapopulations. However, the exact mechanisms by which genetic variation contribute to immune evasion remain unclear. In a study to understand the role of host genetics in disease resistance, a population of pigs were experimentally infected with a type 2 PRRSV isolate. Four pigs that showed virus rebound at 42days post-infection (dpi) were analyzed by 454 sequencing to characterize the rebound quasispecies. Deep sequencing of variable regions in nsp1, nsp2, ORF3 and ORF5 showed the largest number of nucleotide substitutions at day 28 compared to days 4 and 42 post-infection. Differences were also found in genetic variations when comparing tonsil versus serum. The results of dN/dS ratios showed that the same regions evolved under negative selection. However, eight ami...

Nature biotechnology, Jan 7, 2015

Clinical and vaccine immunology : CVI, Jan 7, 2015

Co-infections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine c... more Co-infections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) contribute to a group of disease syndromes known as porcine circovirus associated disease (PCVAD). Presumably, PRRSV infection enhances PCV2 replication as a result of modulation of host immunity. The purpose of this study was to evaluate PCV2 replication and pathogenesis in pigs vaccinated with a PRRS modified live virus (MLV) vaccine and subsequently challenged with a combination of PRRSV and PCV2. During the early post-challenge period, PRRSV-associated clinical signs were decreased and average daily gain (ADG) was increased in the vaccinated group, demonstrating the protective effect of PRRS vaccination. However, during the later post-challenge period, the vaccinated group showed greater numbers of pigs with increased PCV2 viremia, decreased ADG, increased PCVAD clinical signs, and increased mortality. In this disease model, the early benefits of PRRSV vaccina...

Abstract Text: Genetic marker WUR10000125 (WUR) on chromosome 4 has been associated with response... more Abstract Text: Genetic marker WUR10000125 (WUR) on chromosome 4 has been associated with response to Porcine Reproductive and Respiratory Syndrome (PRRS) virus (PRRSV) in growing pigs, but little is known about its association in a co-infection disease model. The objective of this study was to assess the effects of marker WUR and vaccination on nursery pigs co-infected with PRRSV and Porcine Circovirus type-2b (PCV2b). At 28 days prior to infection, 206 commercial Yorkshire*Landrace weaned pigs, preselected to be AA or AB at WUR, were randomly allocated to one of two rooms and pigs in one room were treated with a modified live PRRSV vaccine. At 0 days post-infection (dpi), all piglets were co-infected with PRRSV and PCV2b, and euthanized at 42 dpi. Weekly body weights were used to calculate weight gain (WG) from 0-21 dpi (WG0_21) and 21-42 dpi (WG21_42). Viral load (VL) was calculated as area under the curve of log-transformed viremia for PRRSV (PRRSV_VL) and PCV2b (PCV_VL). WG and ...

Abstract Text: Porcine Reproductive and Respiratory Syndrome (PRRS) and Porcine Circovirus type 2... more Abstract Text: Porcine Reproductive and Respiratory Syndrome (PRRS) and Porcine Circovirus type 2b (PCV2b) are detrimental viral diseases to the porcine industry. A total of 206 weaner piglets were randomly assigned to one of two rooms. Pigs in one room were vaccinated for PRRS and 28 days later, all pigs were co-infected with both viruses. The non-vaccinated piglets were 2.06 times more likely to present with blue ear (p<0.05). The effect of vaccination on Average Daily Gain (ADG) varied over time (p<0.0001). The effects of both WUR genotype, a swine chromosome 4 SNP associated with host response to PRRS, and vaccination on PRRS viremia varied significantly over time (p<0.01). Blue ear and mortality after co-infection had a moderate heritable component. The introduction of PCV2b with PRRS may have diluted the impact of the WUR genotype on host response. Keywords: Porcine Reproductive and Respiratory Syndrome Porcine Circovirus type-2b Host response

Veterinary immunology and immunopathology, Jan 15, 2014

Severe combined immunodeficiency (SCID) is the result of a set of inherited genetic defects which... more Severe combined immunodeficiency (SCID) is the result of a set of inherited genetic defects which render components of the immune response nonfunctional. In Arabian horses, Jack Russell terriers, and mice, the disorder is a consequence of the absence of T and B lymphocytes, while natural killer (NK) cell and other leukocyte populations remain intact. Preliminary analysis of a naturally acquired form of inherited SCID in a line of pigs showed several defects in the architecture and composition of secondary lymphoid organs. In this study, a quantitative assessment of lymphocyte populations in affected and normal littermates showed depleted T or B lymphocyte populations in affected pigs; however, NK cells and neutrophils were present in numbers comparable to unaffected littermates. The results indicate that the immune defect in pigs shares the same features as other SCID-affected species.

Journal of wildlife diseases, 2015

Multiplex serology was performed for the detection of total immunoglobulin (Ig) and IgM antibodie... more Multiplex serology was performed for the detection of total immunoglobulin (Ig) and IgM antibodies against porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and swine influenza virus (SIV) antigens in feral swine (Sus scrofa). Serum samples were collected from the islands of Oahu (292 pigs) and Hawaii (52 pigs) between 2007 and 2010. The highest antibody prevalence was to PCV2 (63%), followed by SIV (7.8%) and PRRSV (5.8%). Antigen-specific IgM was detected at a much lower prevalence. PCR amplification and sequence analysis of PCV2 in three IgM-positive samples identified PCV2b as the only genotype. While the prevalence of PCV2 and PRRSV remained similar between 2007 and 2010, the percentage of SIV-positive samples on Oahu increased from 2% to 19%. Our results demonstrate the utility of multiplex serology for pathogen surveillance in feral pig populations.

BioResearch open access, 2012

Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treat... more Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodeficient pigs were injected subcutaneously in the left ear with human melanoma cells (A375SM cells) and in the right ear with human pancreatic carcinoma cells (PANC-1). All immunodeficient pigs developed tumors that were verified by histology and immunohistochemistry. Nonaffected littermates did not develop tumors. Immunodeficient pigs, which do not reject xenografted human tumors, have the potential to become an extremely useful animal model for cancer therapy because of their similarity in size, anatomy, an...

Vaccine, 2012

Porcine circovirus associated disease (PCVAD) encompasses a group of syndromes linked to infectio... more Porcine circovirus associated disease (PCVAD) encompasses a group of syndromes linked to infection with porcine circovirus type 2 (PCV2). Based on the hypothesis that the immune responses to vaccination versus infection are quantitatively and qualitatively different, the objective of this study was to evaluate immunity, virus replication and disease protection in pigs vaccinated with PCV2 capsid protein (CP) and during infection. The disease model included dual infection with PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV), a virus known to enhance disease progression and severity. The principal effect of PRRSV infection was to increase peak PCV2 viremia by almost 40-fold; however, PCV2 failed to show a reciprocal effect on PRRSV. In vaccinated pigs, there was no evidence of disease or PCV2 replication following dual virus challenge. Immunity following vaccination favored PCV2 neutralizing activity; whereas, PCV2 infection and disease produced high levels of non-neutralizing antibody, primarily directed against a polypeptide in the C-terminal region of CP. These results support the notion that the magnitude of the total antibody response cannot be used as a measure of protective immunity. Furthermore, protection versus disease lies in the immunodominance of specific epitopes. Epitope specificity should be taken into consideration when designing PCV2 vaccines.

BioMed Research International, 2014

Porcine reproductive and respiratory syndrome (PRRS) is a high-consequence animal disease with cu... more Porcine reproductive and respiratory syndrome (PRRS) is a high-consequence animal disease with current vaccines providing limited protection from infection due to the high degree of genetic variation of field PRRS virus. Therefore, understanding host immune responses elicited by different PRRSV strains will facilitate the development of more effective vaccines. Using IngelVac modified live PRRSV vaccine (MLV), its parental strain VR-2332, and the heterologous KS-06-72109 strain (a Kansas isolate of PRRSV), we compared immune responses induced by vaccination and/or PRRSV infection. Our results showed that MLV can provide complete protection from homologous virus (VR-2332) and partial protection from heterologous (KS-06) challenge. The protection was associated with the levels of PRRSV neutralizing antibodies at the time of challenge, with vaccinated pigs having higher titers to VR-2332 compared to KS-06 strain. Challenge strain did not alter the cytokine expression profiles in the serum of vaccinated pigs or subpopulations of T cells. However, higher frequencies of IFN--secreting PBMCs were generated from pigs challenged with heterologous PRRSV in a recall response when PBMCs were re-stimulated with PRRSV. Thus, this study indicates that serum neutralizing antibody titers are associated with PRRSV vaccination-induced protection against homologous and heterologous challenge.

Virus Research, 2008

Genomic sequence analysis demonstrates that porcine circovirus type 2 (PCV2) isolates are divided... more Genomic sequence analysis demonstrates that porcine circovirus type 2 (PCV2) isolates are divided into distinct genotypes. Historically, swine herds in the U.S. have been infected with the PCV2a genotype. In 2005, PCV2b was identified in North America and with it increased reports of porcine circovirus disease (PCVD). A differential PCR technique incorporating PCV2 genotype-specific primers was used in the clinical diagnosis of PCVD. A set of 97 diagnostic submissions showed that both PCV2a and PCV2b were present in 25% of clinical samples. The construction of phylogenetic trees using whole genome sequences from diagnostic submissions showed that one isolate, 0737A, was only loosely associated with other PCV2b isolates. Analysis of the variable sites between representative PCV2a and PCV2b DNA sequences and the 0737A sequence, showed that 0737A was a mosaic sequence, with the ORF1 region from PCV2a and ORF2 from PCV2b. This study demonstrates that pigs can be naturally infected with multiple PCV2 genotypes and that PCV2a/PCV2b recombination events occur in the field.