RESUMO
The Blank Park Zoo began suffering mortalities in the spring of 2012 within a flock of 229 captive budgerigars (Melopsittacus undulatus) housed in an interactive public-feeding aviary. Clinical signs in affected birds included weakness, posterior paresis, inability to fly, or acute death. Gross and microscopic lesions were not initially apparent in acutely affected deceased birds. Many birds had evidence of trauma, which is now hypothesized to have been related to the birds' weakness. Investigation into the cause(s) of morbidity and mortality were complicated by the opening of a new interactive enclosure. For this reason, environmental conditions and husbandry protocols were heavily scrutinized. Microscopic examination of dead budgies later in the course of the investigation revealed mineralization of soft tissues consistent with hypervitaminosis D. Pooled serum analysis of deceased birds identified elevated vitamin D3 levels. Vitamin D3 analysis was performed on the feed sticks offered by the public and the formulated maintenance diet fed to the flock. This analysis detected elevated levels of vitamin D3 that were 22.5-times the manufacturer's labeled content in the formulated diet. These findings contributed to a manufacturer recall of more than 100 formulated diets fed to a wide variety of domestic and captive wild animal species throughout the United States and internationally. This case report discusses the complexities of determining the etiology of a toxic event in a zoologic institution.
Assuntos
Ração Animal/análise , Doenças das Aves/induzido quimicamente , Colecalciferol/efeitos adversos , Overdose de Drogas/veterinária , Melopsittacus , Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais de Zoológico , Doenças das Aves/mortalidade , Doenças das Aves/patologia , Colecalciferol/análise , Colecalciferol/sangue , Dieta/veterinária , Overdose de Drogas/sangue , Overdose de Drogas/mortalidade , Overdose de Drogas/patologia , Iowa/epidemiologiaRESUMO
Pine needle abortion is a naturally occurring condition in free-range cattle caused by the consumption of pine needles from select species of cypress, juniper, pine, and spruce trees. Confirmatory diagnosis of pine needle abortion has previously relied on a combined case history of pine needle consumption and detection of isocupressic acid in a sample from the dam. Stable metabolites of isocupressic acid include agathic acid, dihydroagathic acid, and tetrahydroagathic acid, which have been shown to be present in the serum of mature animals for a few days following consumption of pine needles. As maternal serum is infrequently submitted for diagnosis of cattle abortions, a diagnostic assay capable of confirming isocupressic acid exposure in other matrices would be desirable. To the authors' knowledge, no previous investigations have indicated whether these stable metabolites of isocupressic acid cross the placenta or are detectable in fetal tissues. Therefore, the presence of agathic acid, dihydroagathic acid, and tetrahydroagathic acid was evaluated using gas chromatography-mass spectroscopy on fetal thoracic fluid and stomach contents collected from 2 aborted bovine fetuses with a recent herd history of pine needle consumption by the dams and a subsequent abortion outbreak in the herd. Only tetrahydroagathic acid was detected in the fetal thoracic fluid and fetal stomach contents. The current study encourages diagnosticians to collect fetal thoracic fluids to permit the detection of tetrahydroagathic acid in cases of suspected pine needle abortion.
Assuntos
Aborto Animal/diagnóstico , Aborto Animal/etiologia , Ácidos Carboxílicos/metabolismo , Diterpenos/metabolismo , Pinus/intoxicação , Intoxicação por Plantas/veterinária , Tetra-Hidronaftalenos/metabolismo , Animais , Biomarcadores/metabolismo , Bovinos , Feto/química , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Conteúdo Gastrointestinal/química , Intoxicação por Plantas/diagnóstico , Intoxicação por Plantas/etiologiaRESUMO
The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals, including humans. We evaluated the ability of pigs affected with vaccine-associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD. Vaccinated and challenged (V/C) pigs were administered an inactivated swine δ-cluster H1N2 (MN08) vaccine with an HA similar to pre-2009 seasonal human viruses and challenged with heterologous A(H1N1) pandemic 2009 (H1N1pdm09). Vaccination induced MN08-specific hemagglutination inhibition (HI) antibody but not cross-reacting H1N1pdm09 HI antibody. However, vaccinated pigs demonstrated significantly higher post-challenge anti-H1N1pdm09 serum neutralizing (SN) antibodies at 14 and 21 days post inoculation (dpi) compared to nonvaccinated, challenged pigs (NV/C), indicating a priming effect of the vaccine. Serum and lung whole virus anti-H1N1pdm09 IgG ELISA antibodies in the vaccinated group were significantly higher than the challenge only pigs at all-time points evaluated. Lung IgA ELISA antibodies to both antigens were detected at 2, 5, and 21 dpi in vaccine-primed pigs, contrasted against mucosal ELISA antibody responses detected only at 21 dpi in the naïve-challenged group. Collectively, vaccine-primed pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine levels, indicating VAERD does not adversely affect the induction of an immune response to challenge with heterologous virus despite the severe clinical disease and underlying lung pathology. Thus, original antigenic sin does not appear to be a component of VAERD.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N2/imunologia , Vacinas contra Influenza/imunologia , Infecções Respiratórias/imunologia , Imunidade Adaptativa/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Citocinas/metabolismo , Variação Genética/imunologia , Testes de Inibição da Hemaglutinação , Imunoglobulina G/imunologia , Vacinas contra Influenza/administração & dosagem , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Pandemias , Infecções Respiratórias/virologia , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Vacinação/veterináriaRESUMO
Influenza A viruses cause acute respiratory disease in swine. Viruses with H1 hemagglutinin genes from the human seasonal lineage (δ-cluster) have been isolated from North American swine since 2003. The objective of this work was to study the pathogenesis and transmission of δ-cluster H1 influenza viruses in swine, comparing three isolates from different phylogenetic subclusters, geographic locations, and years of isolation. Two isolates from the δ2 subcluster, A/sw/MN/07002083/07 H1N1 (MN07) and A/sw/IL/00685/05 H1N1 (IL05), and A/sw/TX/01976/08 H1N2 (TX08) from the δ1 sub-cluster were evaluated. All isolates caused disease and were transmitted to contact pigs. Respiratory disease was apparent in pigs infected with MN07 and IL05 viruses; however, clinical signs and lung lesions were reduced in severity as compared to TX08. On day 5 following infection MN07-infected pigs had lower virus titers than the TX08 pigs, suggesting that although this H1N1 was successfully transmitted, it may not replicate as efficiently in the upper or lower respiratory tract. MN07 and IL05 H1N1 induced higher serum antibody titers than TX08. Greater serological cross-reactivity was observed for viruses from the same HA phylogenetic sub-cluster; however, antigenic differences between the sub-clusters may have implications for disease control strategies for pigs.
RESUMO
Rickets can be attributed to nutritional, genetic, hormonal, or toxic disturbances and is classified as a metabolic bone disease. Rickets is most often associated with inappropriate dietary levels of calcium, phosphorus, and/or vitamin D. During a 27-month period (January 2010 through March 2012), the Iowa State University Veterinary Diagnostic Laboratory investigated causes of sudden, unexpected death and lameness in growing pigs throughout the Midwestern United States. Clinical observations from 17 growing pig cases included weakness, lameness, reluctance to move, muscle fasciculations and/or tremors, tetany, and death. Ribs were weak, soft, and bent prior to breaking; rachitic lesions were apparent at costochondral junctions in multiple cases. Acute and/or chronic bone fractures were also noted in multiple bones. Failure of endochondral ossification, expanded physes, infractions, thin trabeculae, and increased osteoclasts were noted microscopically. Decreased bone ash and serum 25(OH)D(3), combined with clinical and microscopic evaluation, confirmed a diagnosis of vitamin D-dependent rickets in all cases. In 3 cases, disease was linked to a specific nutrient supplier that ultimately resulted in a voluntary feed recall; however, most cases in the current investigation were not associated with a particular feed company. The present report describes vitamin D-associated rickets and its importance as a potential cause of weakness, lameness, muscle fasciculations, recumbency or sudden unexpected death in swine, and describes appropriate samples and tests for disease diagnosis.
Assuntos
Raquitismo/veterinária , Doenças dos Suínos/patologia , Deficiência de Vitamina D/veterinária , Envelhecimento , Animais , Raquitismo/sangue , Raquitismo/patologia , Suínos , Doenças dos Suínos/sangue , Deficiência de Vitamina D/sangueRESUMO
Control of swine influenza A virus (IAV) in the United States is hindered because inactivated vaccines do not provide robust cross-protection against the multiple antigenic variants cocirculating in the field. Vaccine efficacy can be limited further for vaccines administered to young pigs that possess maternally derived immunity. We previously demonstrated that a recombinant A/sw/Texas/4199-2/1998 (TX98) (H3N2) virus expressing a truncated NS1 protein is attenuated in swine and has potential for use as an intranasal live attenuated influenza virus (LAIV) vaccine. In the present study, we compared 1 dose of intranasal LAIV with 2 intramuscular doses of TX98 whole inactivated virus (WIV) with adjuvant in weanling pigs with and without TX98-specific maternally derived antibodies (MDA). Pigs were subsequently challenged with wild-type homologous TX98 H3N2 virus or with an antigenic variant, A/sw/Colorado/23619/1999 (CO99) (H3N2). In the absence of MDA, both vaccines protected against homologous TX98 and heterologous CO99 shedding, although the LAIV elicited lower hemagglutination inhibition (HI) antibody titers in serum. The efficacy of both vaccines was reduced by the presence of MDA; however, WIV vaccination of MDA-positive pigs led to dramatically enhanced pneumonia following heterologous challenge, a phenomenon known as vaccine-associated enhanced respiratory disease (VAERD). A single dose of LAIV administered to MDA-positive pigs still provided partial protection from CO99 and may be a safer vaccine for young pigs under field conditions, where dams are routinely vaccinated and diverse IAV strains are in circulation. These results have implications not only for pigs but also for other influenza virus host species.
Assuntos
Anticorpos/química , Vacinas contra Influenza/metabolismo , Infecções Respiratórias/imunologia , Vacinas Atenuadas/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Linhagem Celular , Cães , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H3N2/metabolismo , Pulmão/metabolismo , Mucosa/metabolismo , SuínosRESUMO
Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies.
Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N2/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Pneumonia Viral/veterinária , Doenças dos Suínos/patologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Líquido da Lavagem Broncoalveolar/química , Citocinas/análise , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Pulmão/patologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Índice de Gravidade de Doença , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Eliminação de Partículas ViraisRESUMO
PB2 627K is a determinant of influenza host range and contributes to the pathogenicity of human-, avian-, and mouse-adapted influenza viruses in the mouse model. Here we used mouse and pig models to analyze the contribution of a swine-origin and avian-origin PB2 carrying either 627K or 627E in the background of the classical swine H1N1 (A/Swine/Iowa/15/30; 1930) virus. The results showed PB2 627K is crucial for virulence in the mouse model, independent of whether PB2 is derived from an avian or swine influenza virus (SIV). In the pig model, PB2 627E decreases pathogenicity of the classical 1930 SIV when it contains the swine-origin PB2, but not when it possesses the avian-origin PB2. Our study suggests the pathogenicity of SIVs with different PB2 genes and mutation of codon 627 in mice does not correlate with the pathogenicity of the same SIVs in the natural host, the pig.
Assuntos
Vírus da Influenza A Subtipo H1N1/metabolismo , Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/virologia , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Cães , Regulação Viral da Expressão Gênica/fisiologia , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Vírus Reordenados , Suínos , Virulência/genética , Replicação ViralRESUMO
On 11 June 2009, the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) virus is the predominant influenza virus strain in the human population. It has also crossed the species barriers and infected turkeys and swine in several countries. Thus, the development of a vaccine that is effective in multiple animal species is urgently needed. We have previously demonstrated that the introduction of temperature-sensitive mutations into the PB2 and PB1 genes of an avian H9N2 virus, combined with the insertion of a hemagglutinin (HA) tag in PB1, resulted in an attenuated (att) vaccine backbone for both chickens and mice. Because the new pandemic strain is a triple-reassortant (TR) virus, we chose to introduce the double attenuating modifications into a swine-like TR virus isolate, A/turkey/OH/313053/04 (H3N2) (ty/04), with the goal of producing live attenuated influenza vaccines (LAIV). This genetically modified backbone had impaired polymerase activity and restricted virus growth at elevated temperatures. In vivo characterization of two H1N1 vaccine candidates generated using the ty/04 att backbone demonstrated that this vaccine is highly attenuated in mice, as indicated by the absence of signs of disease, limited replication, and minimum histopathological alterations in the respiratory tract. A single immunization with the ty/04 att-based vaccines conferred complete protection against a lethal H1N1pdm virus infection in mice. More importantly, vaccination of pigs with a ty/04 att-H1N1 vaccine candidate resulted in sterilizing immunity upon an aggressive intratracheal challenge with the 2009 H1N1 pandemic virus. Our studies highlight the safety of the ty/04 att vaccine platform and its potential as a master donor strain for the generation of live attenuated vaccines for humans and livestock.
Assuntos
Vírus da Influenza A Subtipo H3N2/genética , Vacinas contra Influenza/genética , Infecções por Orthomyxoviridae/imunologia , RNA Polimerase Dependente de RNA/genética , Vacinas Atenuadas/genética , Proteínas Virais/genética , Animais , Linhagem Celular , Humanos , Imunização , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Camundongos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/veterinária , Pandemias , Vírus Reordenados/enzimologia , Vírus Reordenados/genética , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/prevenção & controle , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologiaRESUMO
Triple-reassortant swine influenza viruses circulating in North American pigs contain the internal genes derived from swine (matrix, non-structural and nucleoprotein), human [polymerase basic 1 (PB1)] and avian (polymerase acidic and PB2) influenza viruses forming a constellation of genes that is well conserved and is called the triple-reassortant internal gene (TRIG) cassette. In contrast, the external genes [haemagglutinin (HA) and neuraminidase (NA)] are less conserved, reflecting multiple reassortant events that have produced viruses with different combinations of HA and NA genes. This study hypothesized that maintenance of the TRIG cassette confers a selective advantage to the virus. To test this hypothesis, pigs were co-infected with the triple-reassortant H3N2 A/Swine/Texas/4199-2/98 (Tx/98) and the classical H1N1 A/Swine/Iowa/15/1930 viruses and co-housed with a group of sentinel animals. This direct contact group was subsequently moved into contact with a second group of naïve animals. Four different subtypes (H1N1, H1N2, H3N1 and H3N2) of influenza virus were identified in bronchoalveolar lavage fluid collected from the lungs of the experimentally infected pigs, with most of the viruses containing TRIG from the Tx/98 virus. Interestingly, only the intact H3N2 Tx/98 virus was transmitted from the infected pigs to the direct-contact animals and from them to the second contact group of pigs. These results demonstrated that multiple reassortments can occur within a host; however, only specific gene constellations are readily transmissible. It was concluded that certain HA and NA gene pairs, in conjunction with the TRIG cassette, may have a competitive advantage over other combinations for transmission and maintenance in swine.
Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/patogenicidade , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/genética , Vírus Reordenados/patogenicidade , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia , Animais , Genes Virais , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Pulmão/virologia , Neuraminidase/genética , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/isolamento & purificação , Sus scrofa , SuínosRESUMO
The gene constellation of the 2009 pandemic A/H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species. Although its hemagglutinin gene is related to North American H1 SIV, it is unknown if vaccines currently used in U.S. swine would cross-protect against infection with the pandemic A/H1N1. The objective of this study was to evaluate the efficacy of inactivated vaccines prepared with North American swine influenza viruses as well as an experimental homologous A/H1N1 vaccine to prevent infection and disease from 2009 pandemic A/H1N1. All vaccines tested provided partial protection ranging from reduction of pneumonia lesions to significant reduction in virus replication in the lung and nose. The multivalent vaccines demonstrated partial protection; however, none was able to prevent all nasal shedding or clinical disease. An experimental homologous 2009 A/H1N1 monovalent vaccine provided optimal protection with no virus detected from nose or lung at any time point in addition to amelioration of clinical disease. Based on cross-protection demonstrated with the vaccines evaluated in this study, the U.S. swine herd likely has significant immunity to the 2009 A/H1N1 from prior vaccination or natural exposure. However, consideration should be given for development of monovalent homologous vaccines to best protect the swine population thus limiting shedding and the potential transmission of 2009 A/H1N1 from pigs to people.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Proteção Cruzada , Pulmão/patologia , Pulmão/virologia , Nariz/virologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Suínos , Vacinas de Produtos Inativados/imunologia , Eliminação de Partículas ViraisRESUMO
BACKGROUND: A novel A/H1N1 was identified in the human population in North America in April 2009. The gene constellation of the virus was a combination from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before been identified in swine or other species. OBJECTIVES: The objectives were to (i) evaluate the clinical response of swine following experimental inoculation with pandemic H1N1 2009; (ii) assess serologic cross-reactivity between H1N1 2009 and contemporary SIV antisera; and (iii) develop a molecular assay to differentiate North American-lineage SIV from H1N1 2009. METHODS: Experiment 1: Weaned pigs were experimentally infected with A/California/04/2009 (H1N1). Experiment 2: The cross-reactivity of a panel of US SIV H1N1 or H1N2 antisera with three isolates of pandemic A/H1N1 was evaluated. Experiment 3: A polymerase chain reaction (PCR)-based diagnostic test was developed and validated on samples from experimentally infected pigs. RESULTS AND CONCLUSIONS: In experiment 1, all inoculated pigs demonstrated clinical signs and lesions similar to those induced by endemic SIV. Viable virus and antigen were only detected in the respiratory tract. In experiment 2, serologic cross-reactivity was limited against H1N1 2009 isolates, notably among virus antisera from the same HA phylogenetic cluster. The limited cross-reactivity suggests North American pigs may not be fully protected against H1N1 2009 from previous exposure or vaccination and novel tests are needed to rapidly diagnose the introduction of H1N1 2009. In experiment 3, an RT-PCR test that discriminates between H1N1 2009 and endemic North American SIV was developed and validated on clinical samples.
Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/imunologia , Animais , Anticorpos Antivirais/imunologia , Reações Cruzadas , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , América do Norte , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Suínos , Doenças dos Suínos/virologiaRESUMO
A highly virulent H1N1 influenza A virus, A/Swine/Kansas/77778/2007 (KS07), which caused approximately 10% mortality in finishing pigs, was isolated from herds in the Midwestern United States. Molecular and phylogenic analysis revealed this swine isolate was a triple reassortant virus, similar to an H1N1 virus that infected humans and pigs at an Ohio county fair in August 2007. A pig challenge model was developed to evaluate the pathogenicity and transmission capacity of the KS07 virus. The results confirmed that the KS07 virus is highly virulent in pigs and easily transmitted to sentinel animals. The KS07 virus failed to cross-react with a panel of H1-specific swine sera. Interestingly, the KS07 virus shed for a prolonged period up to 7 days in infected pigs, indicating that this virus can spread efficiently between animals. The highly virulent H1N1 swine influenza virus is further evidence of reassortment among avian, human and swine influenza viruses and justifies the need for continued surveillance of influenza viruses in swine.
Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/fisiologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/transmissão , Animais , Antígenos Virais/imunologia , Linhagem Celular , Reações Cruzadas , Cães , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/transmissão , Filogenia , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/imunologia , Estados Unidos/epidemiologia , VirulênciaRESUMO
Two novel paramyxoviruses, 81-19252 (Texas81) and 92-7783 (ISU92), isolated from the brains of pigs in the United States in the 1980s and 1990s, were characterized. The complete genome of Texas81 virus was 15,456 nucleotides (nt) in length, that of ISU92 was 15,480 nt, and both genomes consisted of six nonoverlapping genes, predicted to encode nine proteins, with conserved and complementary 3' leader and 5' trailer regions and conserved gene starts, gene stops, and trinucleotide intergenic sequences similar to those in paramyxoviruses. The corresponding genes from these two viruses were similar in length, except for the F genes, of which the ISU92 form had an additional 24-nt U-rich 3' untranslated region. The P genes of swine viruses were predicted to produce V and D mRNAs by RNA editing (one to four G insertions in Texas81 and one to nine G insertions in ISU92) or C mRNA by alternative translation initiation. Sequence-specific features related to virus replication and host-specific amino acid signatures indicated that these viruses originated from bovine parainfluenzavirus 3 (bPIV3). Phylogenetic analysis of individual genes suggested that these viruses are novel members of the genus Respirovirus of the Paramyxovirinae subfamily and may be grouped into two subgenotypes of genotype A of bPIV3. Our comprehensive studies revealed that these swine PIV3 are variants of bPIV3 and were possibly transferred from cattle to pigs but failed to establish an active enzootic state. These two viruses were mildly pathogenic to conventionally reared pigs, and results from a limited enzyme-linked immunosorbent assay-based serosurvey of swine farms in Minnesota and Iowa in 2007 and 2008 were negative.
Assuntos
Genoma Viral , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae , Análise de Sequência de DNA , Doenças dos Suínos/virologia , Animais , Dados de Sequência Molecular , Paramyxoviridae/classificação , Paramyxoviridae/genética , Paramyxoviridae/isolamento & purificação , Paramyxoviridae/patogenicidade , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Filogenia , Prevalência , Suínos , Doenças dos Suínos/epidemiologia , Estados Unidos/epidemiologia , Proteínas Virais/genética , VirulênciaRESUMO
A swine influenza virus (SIV) vaccine-challenge pig model was used to study the potential of a conserved matrix 2 (M2) protein vaccine alone or in combination with an inactivated H1N1-vaccine to protect against H1N1 and H1N2 viruses. The H1N1-vaccine and heterologous H1N2-challenge virus model has previously been shown to prolong fever and increase SIV-associated pneumonic lesions. The M2 vaccine in combination with the H1N1-vaccine reduced the H1N2 induced fever but not virus shedding. The M2 vaccine alone reduced respiratory signs and pneumonic lesions to levels similar to the negative control pigs following H1N2 infection. This study found that the M2 protein has potential as a vaccine for SIV-associated disease prevention. However, development of an immune response towards the major envelope HA protein was required to reduce SIV shedding.
Assuntos
Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N2/imunologia , SuínosRESUMO
The objective of this study was to assess the effect of concurrent infection with porcine reproductive and respiratory syndrome virus (PRRSV) on the efficacy of an inactivated swine influenza virus (SIV) vaccine. Eight groups of pigs were infected with a virulent PRRSV isolate either between the two SIV vaccines or at the time of SIV challenge. Control groups included SIV vaccination without PRRSV and pigs infected with SIV and/or PRRSV. Pigs infected with PRRSV during vaccination showed increased levels of macroscopic and microscopic lesions compared to pigs vaccinated against and challenged with only SIV indicating decreased SIV vaccine efficacy. In addition, pigs vaccinated in the presence of PRRSV showed increased clinical disease and shedding of SIV during the acute phase of SIV infection. No alterations in the systemic or local antibody response to either SIV vaccination or challenge were observed. These findings demonstrate that PRRSV infection has a significant impact on SIV vaccine efficacy that may be important for disease control.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Síndrome Respiratória e Reprodutiva Suína/imunologia , Sus scrofa , Doenças dos Suínos/prevenção & controle , Animais , Anticorpos Antivirais/análise , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Doenças dos Suínos/imunologiaRESUMO
Tissue samples from 2 juvenile ferrets (Mustela putorius furo) from a colony that was undergoing an outbreak of respiratory disease were submitted to the Iowa State University Veterinary Diagnostic Laboratory. Microscopic examination of lung samples revealed bronchointerstitial pneumonia with necrotizing bronchiolitis. Influenza A virus was detected in sections of formalin-fixed lung by immunohistochemistry and reverse transcription polymerase chain reaction assay. A field investigation of the premises and analysis of additional samples led to the confirmation and characterization of an influenza virus with high homology to contemporary reassortant H1N1 swine influenza viruses. Although ferrets have been used extensively to research the virulence and transmissibility of avian, human, and swine influenza virus strains, no published information exists on naturally occurring outbreaks of swine influenza in ferrets.
Assuntos
Furões , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Infecções por Orthomyxoviridae/veterinária , Animais , Infecções por Orthomyxoviridae/virologia , FilogeniaRESUMO
H1 influenza A viruses that were distinct from the classical swine H1 lineage were identified in pigs in Canada in 20032004; antigenic and genetic characterization identified the hemagglutinin (HA) as human H1 lineage. The viruses identified in Canadian pigs were human lineage in entirety or double (humanswine) reassortants. Here, we report the whole genome sequence analysis of four human-like H1 viruses isolated from U.S. swine in 2005 and 2007. All four isolates were characterized as triple reassortants with an internal gene constellation similar to contemporary U.S. swine influenza virus (SIV), with HA and neuraminidase (NA) most similar to human influenza virus lineages. A 2007 human-like H1N1 was evaluated in a pathogenesis and transmission model and compared to a 2004 reassortant H1N1 SIV isolate with swine lineage HA and NA. The 2007 isolate induced disease typical of influenza virus and was transmitted to contact pigs; however, the kinetics and magnitude differed from the 2004 H1N1 SIV. This study indicates that the human-like H1 SIV can efficiently replicate and transmit in the swine host and now co-circulates with contemporary SIVs as a distinct genetic cluster of H1 SIV.
Assuntos
Genoma Viral , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N2/genética , Infecções por Orthomyxoviridae/veterinária , Análise de Sequência de DNA , Doenças dos Suínos/virologia , Suínos/virologia , Animais , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/patogenicidade , Dados de Sequência Molecular , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , RNA Viral/genética , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Estados UnidosRESUMO
Two swine paramyxoviruses (SPMV)-(81-19252 (Texas-81) and 92-7783 (ISU-92)-were isolated from encephalitic pigs in the United States in 1981 and 1992. Antigenic, morphologic, and biological characteristics of these two viruses were essentially similar to members of the family Paramyxoviridae. Antigenic analysis by indirect fluorescent antibody, immunoblot, and one-way cross-neutralization tests placed these viruses along with bovine parainfluenza 3 (BPIV3) viruses. Purified virions were 50-300 nm in size and morphologically indistinguishable from other paramyxoviruses. These two viruses hemagglutinated red blood cells and had neuraminidase activity. The gene junctions of fusion (F) and hemagglutinin (HN) glycoprotein genes of these viruses contained highly conserved transcription start and stop signal sequences and trinucleotide intergenic regions similar to other Paramyxoviridae. The F gene of ISU-92 was longer than Texas-81 due to insertion of a 24-nucleotide "U"-rich 3' untranslated region. Structure-based sequence alignment of glycoproteins of these two SPMVs indicated that they are essentially similar in structure and function to parainfluenzaviruses. The Texas-81 strain was closely related to BPIV3 Shipping Fever (SF) strain at nucleotide and amino acid level, while the ISU-92 strain was more closely related to BPIV3 910N strain. The envelope glycoproteins of ISU-92 had only approximately 92 and approximately 96% identity at nucleotide and amino acid levels with BPIV3-SF strain, respectively. The high sequence identities to BPIV3 indicated cross-species infection in pigs. Phylogenetic analyses based on both F protein and HN protein suggested the classification of these viruses into the subfamily Paramyxovirinae, genus Respirovirus, and genotype A of BPIV3.
Assuntos
Glicoproteínas/genética , Infecções por Paramyxoviridae/veterinária , Paramyxoviridae/classificação , Paramyxoviridae/genética , Filogenia , Doenças dos Suínos/virologia , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Análise por Conglomerados , Proteína HN/genética , Proteína HN/metabolismo , Hemaglutinação , Dados de Sequência Molecular , Neuraminidase/metabolismo , Paramyxoviridae/imunologia , Paramyxoviridae/isolamento & purificação , Infecções por Paramyxoviridae/virologia , RNA Viral/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Sorotipagem , Suínos , Estados Unidos , Vírion/ultraestruturaRESUMO
Influenza is a zoonotic viral disease that represents a health and economic threat to both humans and animals worldwide. Swine influenza (SI) was first recognized clinically in pigs in the Midwestern U.S., in 1918, coinciding with the human influenza pandemic known as the Spanish flu. Since that time SI has remained of importance to the swine industry throughout the world. In this review, the epidemiology of swine influenza virus (SIV) infection in North American pigs is described in detail. The first 80 years of SI remained relatively static, whereas the last decade has become dynamic with the establishment of many emerging subtypes. With the increasing number of novel subtypes and genetic variants, the control of SI has become increasingly difficult and innovative strategies to combat this economically important zoonotic disease are critical. Therefore, protective immune responses against influenza virus infections as well as new paradigms of vaccine development in pigs are discussed in the review. It is expected that the dynamic evolutionary changes of SIVs in North American pigs will continue, making currently available prophylactic approaches of limited use to control the spread and economic losses associated with this important swine pathogen.