Goodrich LR, McIlwraith CW, Grieger J, Kraus VB, Stabler T, Werpy N, Phillips J, Samulski RJ, Frisbie D.To evaluate the effects of a gene transfer approach to IL-1β inhibition in an equine osteochondral chip fragment model of joint injury using a self-complementary adeno-associated virus with interleukin receptor antagonist transgene cassette (scAAVIL-1ra), as posttraumatic osteoarthritis in horses, similar to people, is a significant clinical problem. Methods: 16 horses were utilized for the study. Methods: All horses had an osteochondral chip fragment induced arthroscopically in one middle carpal joint while the contralateral joint was sham operated. Eight horses received either scAAVIL-1ra o...
Taesuji M, Rattanamas K, Yim PB, Ruenphet S.The Flinders Technology Associates (FTA) card, a cotton-based cellulose membrane impregnated with a chaotropic agent, effectively inactivates infectious microorganisms, lyses cellular material, and fixes nucleic acid. The aim of this study is to assess the stability and detection limit of various RNA viruses, especially the avian influenza virus (AIV), Newcastle disease virus (NDV), and African horse sickness virus (AHSV), on the FTA card, which could significantly impact virus storage and transport practices. To achieve this, each virus dilution was inoculated onto an FTA card and stored at r...
Equine hepacivirus (EqHV, , hepacivirus) is a small, enveloped RNA virus generally causing sub-clinical hepatitis with occasional fatalities. EqHV is reported in equids worldwide, but for Italy data are limited. To address this, a survey study was set up to estimate prevalence at a national level and among different production categories (equestrian; competition; work and meat; reproduction) and national macro-regions (North, Central, South, and Islands). Data obtained testing 1801 horse serum samples by Real-Time RT PCR were compared within the categories and regions. The NS3 fragment of the ...
de la Cuesta-Torrado M, Velloso Alvarez A, Neira-Egea P, Cuervo-Arango J.Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population. Objective: Study the influence of EHM on the likelihood of affected horses to return to their previous performance and investigate the association of clinical variables with prognosis. Methods: Twenty-six horses positive for equine herpesvirus type 1 (EHV-1) were admitted to a veterinary teaching hospital (VTH) during a natural EHM outbreak at an international jumping event. Methods: Data collected from the VTH, the International Equestrian Federation, and surveys completed by the riders and horse own...
Tanaka Y, Watanabe K, Takeyama A, Tagami M, Hamano H, Fukumoto N, Nambo Y, Kobayashi Y.Equine testicular arteritis commonly occurs as a consequence of the migration of nematode larvae or equine arteritis virus (EAV) infection. However, testicular arteritis without evidence of these infections has been reported, and the underlying pathogenesis remains unclear. We encountered testicular arteritis without evidence of nematode or EAV infection in a 3-year-old male heavy draft horse with scrotal enlargement. Grossly, the volume of the pampiniform plexus was markedly increased due to edema. Histologically, non-suppurative and necrotizing testicular arteritis, characterized by lymphocy...
Wilkin T, Hamilton NA, Cawley AT, Bhat S, Baoutina A.The term 'gene doping' is used to describe the use of any unauthorized gene therapy techniques. We developed a test for five likely candidate genes for equine gene doping: , , , and . The test is based on real-time polymerase chain reaction (PCR) and includes separate screening and confirmation assays that detect different unique targets in each transgene. For doping material, we used nonviral (plasmid) and viral (recombinant adeno-associated virus) vectors carrying complementary DNA for the targeted genes; the vectors were accurately quantified by digital PCR. To reduce non-specific amplific...
Bernard C, Joly Kukla C, Rakotoarivony I, Duhayon M, Stachurski F, Huber K, Giupponi C, Zortman I, Holzmuller P, Pollet T, Jeanneau M, Mercey A....Crimean-Congo haemorrhagic fever (CCHF), a potentially severe zoonotic viral disease causing fever and haemorrhagic manifestations in humans. As the Crimean-Congo haemorrhagic fever virus (CCHFV) has been detected in ticks in Spain and antibodies against the virus in ruminant sera in Corsica, it was necessary to know more about the situation in France. In 2022-2023, CCHFV was detected in 155 ticks collected from horses and cattle in southern France.
Tirosh-Levy S, Shaiman Barom L, Novak S, Eyngor M, Schvartz G, Yakobson B, Steinman A.Rabies is a fatal zoonotic disease affecting all mammalian species. It is caused by the rabies virus and is prevalent worldwide. Horses are not commonly infected with rabies but their vaccination is recommended due to the potential zoonotic risk. This study aimed to evaluate the duration of immunity following rabies vaccination in horses. A total of 126 serum samples were collected from 93 horses, vaccinated 6 to 91 months before sampling. Rabies-virus-neutralizing antibody (RVNA) levels were evaluated using the Rabies Fluorescent Focus Inhibition Test (RFFIT). A protective RVNA titer of above...
Zhang Z, Guo K, Chu X, Liu M, Du C, Hu Z, Wang X.Equine infectious anemia (EIA) is a contagious disease of horses caused by the equine infectious anemia virus (EIAV). The clinical signs at the acute phase include intermittent high fever, thrombocytopenia, hemorrhage, edema, and anemia. The clinical signs at chronic and relapsing subclinical levels include emaciation and progressive weakness. Surviving horses become lifelong carriers because of the integration of the viral genome into that of the host, and these horses can produce and transmit the virus to other animals. This increases the difficulty of imposing practical control measures to ...
El-Zayat M, Shemies OA, Mosad SM, El Rahman SA.Equine herpes viruses (EHVs) are considered one of the most important respiratory pathogens in equids, resulting in serious outcomes for equine health worldwide. The objectives of the current research were the detection, molecular characterization, and isolation of EHV-1 and EHV-4 circulating within different equine populations in Egypt, either clinically or in apparently healthy horses. Unassigned: A total of 120 field samples were collected, and DNA was extracted. Screening and typing of extracted DNA were done by consensus and conventional PCR assays for detection of EHV-1 and EHV-4, follow...
Kreutzfeldt N, Chambers TM, Reedy S, Spann KM, Pusterla N.Dexamethasone is routinely administered to horses but its effect on the antibody response to a commercial EIV/EHV vaccine is unclear. Objective: Horses receiving dexamethasone will have lower postvaccination antibody levels against EIV and EHV-1 than vaccinated controls. Methods: Fifty-five healthy adult research horses. Methods: Randomized cohort study. Control (no vaccine, group 1), vaccination only (EIV/EHV-1/EHV-4, Prestige 2, Merck Animal Health, group 2), vaccination and concurrent single intravenous dose of dexamethasone (approximately .05 mg/kg, group 3), vaccination and 3 intravenou...
Virtanen J, Hautala K, Utriainen M, Dutra L, Eskola K, Airas N, Uusitalo R, Ahvenainen E, Smura T, Sironen T, Vapalahti O, Kant R, Virtala AK....Parapoxviruses (PPV) cause skin and mucous membrane lesions in several animal species, and of the five recognized PPVs, at least three are zoonotic. Equine PPV (EqPPV) is the sixth one initially described in humans in the United States and later in a severely sick horse in Finland in 2013-2015. In 2021-2022, a large-scale pustulo-vesicular pastern dermatitis outbreak occurred in horses all over Finland. This study aimed at analysing the outbreak, identifying and describing the causative agent, describing clinical signs, and searching for risk factors. EqPPV was identified as a probable causati...
Kaps M, Wenderoth J, Aurich J, Aurich C.Equine viral arteritis (EVA) can induce a persistent carrier state in stallions which then shed the virus via semen. About 30 years ago, obligatory EVA testing of stallions used for artificial insemination (AI) was implemented in the European Union. Information on the efficacy of these regulations on the prevalence of EVA in stallions are not yet available. Therefore, we retrospectively analyzed results of serological and virus antigen testing for EVA in sires of different age and breed referred to Vetmeduni Vienna for semen preservation or veterinary diagnostic procedures between 2001 and 202...
u0130ncili CA, Eru00f6ksu00fcz Y, Otlu B, Kara E, Tanru0131verdi ES, Timurkan Mu00d6, Kalender H, Eru00f6ksu00fcz H. is a Gram-negative, facultative anaerobic bacillus of family, and it is an uncommon pathogen in domestic animals. To date, five cases were reported including two dogs, two cattle, and a goat. is the second common bacterial agent after the . subsp in equine pneumonia cases. The present report describes the isolation of . from lungs and spleen of a 10-year-old Arabian horse (May 08, 2022) at post-mortem examination being co-infected with Clinical and pathological findings included bilateral nasal discharge, conjunctivitis, sternal recumbency, severe diffuse necrosuppurative rhinitis, multi...
Pusterla N, Dorman DC, Burgess BA, Goehring L, Gross M, Osterrieder K, Soboll Hussey G, Lunn DP.Equine herpesvirus type 1 (EHV-1) infection is associated with upper respiratory disease, EHM, abortions, and neonatal death. Objective: Are nasal secretions a more sensitive biological sample compared to blood for the detection of EHV-1 infection? How long is EHV-1 detectable after primary infection by PCR? Methods: MedLine and Web of Science searches identified original peer-reviewed reports evaluating nasal shedding and viremia using virus isolation methods or PCR published in English before October 9, 2023. Results: Sixty experimental and 20 observational studies met inclusion criteria. EH...
Soboll-Hussey G, Dorman DC, Burgess BA, Goehring L, Gross P, Neinast C, Osterrieder K, Pusterla N, Lunn DP.Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. Objective: To determine if there is an association between the level and duration of EHV-1 viremia and either abortion or equine herpesvirus myeloencephalopathy (EHM) in domesticated horses? Methods: A systematic review was performed searching numerous databases to identify peer reviewed reports that evaluated viremia and EHM, or viremia and abortion published before January 19, 2021. Randomized controlled trials and observational studies wer...
Ledbetter EC, Cutler TJ, Irby NL.The aim of this study was to describe the clinical, confocal microscopic, histologic, and virologic features of horses with macrodendritic ulcerative keratitis and conjunctival lymphoid hyperplasia associated with equine herpesvirus-2 and equine herpesvirus-5 infection. Methods: Four foals with bilateral ocular disease. Methods: Complete ophthalmic examination was performed for each horse, and corneal samples were collected for cytology and microbiologic evaluation, including virus isolation and molecular diagnostics for the equine herpesviruses. In vivo confocal microscopy examination of the...
Emelogu U, Lewin AC, Balasuriya UBR, Liu CC, Wilkes RP, Zhang J, Mills EP, Carter RT.Equid alphaherpesvirus 1 (EHV-1) is a global viral pathogen of domestic equids which causes reproductive, respiratory and neurological disease. Few isolates acquired from naturally infected USA-based hosts have been fully sequenced and analyzed to date. An ORF 30 (DNA polymerase) variant (A2254G) has previously been associated with neurological disease in host animals. The purpose of this study was to perform phylogenomic analysis of EHV-1 isolates acquired from USA-based hosts and compare these isolates to previously sequenced global isolates. Methods: EHV-1 was isolated from 23 naturally inf...
Di Genova C, Sutton G, Paillot R, Temperton N, Pronost S, Scott SD.Infection with equid herpesvirus 1 (EHV-1), a DNA virus of the Herpesviridae family represents a significant welfare issue in horses and a great impact on the equine industry. During EHV-1 infection, entry of the virus into different cell types is complex due to the presence of twelve glycoproteins (GPs) on the viral envelope. To investigate virus entry mechanisms, specific combinations of GPs were pseudotyped onto lentiviral vectors. Pseudotyped virus (PV) particles bearing gB, gD, gH and gL were able to transduce several target cell lines (HEK293T/17, RK13, CHO-K1, FHK-Tcl3, MDCK I & II)...
Salgado CRS, Silva ADNE, Arruda IF, Millar PR, Amendoeira MRR, Leon LAA, Teixeira RBC, de Lima JTB, Chalhoub FLL, Bispo de Filippis AM, Fonseca ABM....Hepatitis E virus (HEV) infection has been demonstrated in various animal species; those recognized as potential zoonotic reservoirs pose a considerable risk to public health. In Brazil, HEV-3 is the only genotype identified in humans and swine nationwide, in a colony-breeding cynomolgus monkey and, recently, in bovines and capybara. There is no information regarding HEV exposure in the equine population in Brazil. This study aimed to investigate anti-HEV antibodies and viral RNA in serum samples from horses slaughtered for meat export and those bred for sport/reproduction purposes. We used a ...
Schneider C, James K, Craig BW, Chappell DE, Vaala W, van Harreveld PD, Wright CA, Barnum S, Pusterla N.Equine rhinitis B virus is a lesser-known equine respiratory pathogen that is being detected with increasing frequency via a voluntary upper respiratory biosurveillance program in the United States. This program received 8684 nasal swab submissions during the years 2012-2023. The nasal swabs were submitted for qPCR testing for six common upper respiratory pathogens: subspecies (), equine influenza virus (EIV), equine herpesvirus type 1 (EHV-1), equine herpesvirus type 4 (EHV-4), equine rhinitis A virus (ERAV), and equine rhinitis B virus (ERBV). The overall ERBV qPCR-positivity rate was 5.08...
Osterrieder K, Dorman DC, Burgess BA, Goehring LS, Gross P, Neinast C, Pusterla N, Hussey GS, Lunn DP.Equine herpes virus type 1 (EHV-1) infection in horses is associated with respiratory and neurologic disease, abortion, and neonatal death. Objective: Vaccines decrease the occurrence of clinical disease in EHV-1-infected horses. Methods: A systematic review was performed searching multiple databases to identify relevant studies. Selection criteria were original peer-reviewed research reports that investigated the in vivo use of vaccines for the prevention of disease caused by EHV-1 in domesticated horses. Main outcomes of interest included pyrexia, abortion, neurologic disease, viremia, and n...
Stejskalova K, Janova E, Splichalova P, Futas J, Oppelt J, Vodicka R, Horin P.Toll-like receptors (TLRs) represent an important part of the innate immune system. While human and murine TLRs have been intensively studied, little is known about TLRs in non-model species. The order Perissodactyla comprises a variety of free-living and domesticated species exposed to different pathogens in different habitats and is therefore suitable for analyzing the diversity and evolution of immunity-related genes. We analyzed TLR genes in the order Perissodactyla with a focus on the family Equidae. Twelve TLRs were identified by bioinformatic analyses of online genomic resources; their ...
Kawanishi N, Kinoshita Y, Kambayashi Y, Bannai H, Tsujimura K, Yamanaka T, Cullinane A, Nemoto M.Equine influenza virus (EIV) infection is one of the most important respiratory diseases in the equine industry around the world. Rapid diagnosis, facilitated by point-of-care testing, is essential to implement movement restrictions and control disease outbreaks. This study evaluated a microfluidic immunofluorescence assay kit, which detects influenza virus and SARS-CoV-2 antigens in human specimens with a 12 min turnaround time, for its potential use in detecting EIV. The microfluidic immunofluorescence assay kit succeeded in detecting 11 EIV strains. Using the real-time reverse transcription...
Lim SI, Kim MJ, Kim MJ, Lee SK, Yang HS, Kwon M, Lim EH, Ouh IO, Kim EJ, Hyun BH, Lee YH.Equine influenza virus (EIV) causes acute respiratory disease in horses and belongs to the influenza A virus family , genus . This virus may have severe financial implications for the horse industry owing to its highly contagious nature and rapid transmission. In the Republic of Korea, vaccination against EIV has been practiced with the active involvement of the Korea Racing Authority since 1974. In this study, we monitored the viral RNA for EIV using PCR, as well as the antibody levels against 'A/equine/South Africa/4/03 (H3N8, clade 1)', from 2020 to 2022. EIV was not detected using RT-PCR. ...
Khan Y, Kassymbekov Y, Suleimenova S, Karamendin K, Sabyrzhan T, Nuralibekov S, Daulbayeva K, Abishov A, Akhmetzhanova M, Akhmetsadykov N, Batanova Z....An influenza virus strain, A/equine/Almaty/268/2020, was isolated from horses in southeast Kazakhstan in 2020. Here, we present the nearly complete genome sequence of this epidemic strain. This study was aimed at obtaining the complete genome sequence of the isolate.
Lawton K, Runk D, Hankin S, Mendonsa E, Hull D, Barnum S, Pusterla N.The aim of this study was to use environmental sampling to determine the frequency of detection of selected equine respiratory viruses and bacteria in horses attending a multi-week equestrian show during the winter months. At four time points during showing, environmental sponge samples were collected from all stalls on the property and tested for the presence of equine herpesvirus-1 (EHV-1), EHV-2, EHV-4, equine influenza virus (EIV), equine rhinitis B virus (ERBV), ss. (), and ss. () using real-time PCR (PCR). Environmental sponges were collected from all 53 barns by using one sponge for...
Li S, Guo K, Wang X, Lin Y, Wang J, Wang Y, Du C, Hu Z, Wang X.Equine infectious anemia (EIA) has a worldwide distribution and causes severe economic losses to the equine industry. The EIA virus (EIAV) genome sequences from different countries are highly diverse, which poses a great challenge for pathogen identification with PCR. Phylogenetic analysis showed that although gag is the most conserved structural gene, it still has great genome variability. Currently, most existing PCR methods are designed based on the gag gene sequence and therefore do not cover all the viral strains, especially Asian EIAV strains. In this study, we developed a tat-gag-based ...
Garcu00eda-Carrasco JM, Muu00f1oz AR, Olivero J, Segura M, Garcu00eda-Bocanegra I, Real R.BackgroundWest Nile virus (WNV) is a flavivirus with an enzootic cycle between birds and mosquitoes; humans and horses are incidental dead-end hosts. In 2020, the largest outbreak of West Nile virus infection in the Iberian Peninsula occurred, with 141 clusters in horses and 77 human cases.AimWe analysed which drivers influence spillover from the cycle to humans and equines and identified areas at risk for WNV transmission.MethodsBased on data on WNV cases in horses and humans in 2020 in Portugal and Spain, we developed logistic regression models using environmental and anthropic variables to ...
de Heus P, Bagu00f3 Z, Weidinger P, Lale D, Trachsel DS, Revilla-Fernu00e1ndez S, Matiasek K, Nowotny N.As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, , Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encephalitis viruses with RT-qP...
Connor RJ, Kawaoka Y, Webster RG, Paulson JC.The receptor specificity of 56 H2 and H3 influenza virus isolates from various animal species has been determined to test the relevance of receptor specificity to the ecology of influenza virus. The results show that the receptor specificity of both H2 and H3 isolates evaluated for sialic acid linkage specificity and inhibition of hemagglutination by horse serum correlates with the species of origin, as postulated earlier for H3 strains based on a limited survey of five human, three avian, and one equine strain. Elucidation of the amino acid sequence of several human H2 receptor variants and a...
Murray K, Selleck P, Hooper P, Hyatt A, Gould A, Gleeson L, Westbury H, Hiley L, Selvey L, Rodwell B.A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
Suzuki Y, Ito T, Suzuki T, Holland RE, Chambers TM, Kiso M, Ishida H, Kawaoka Y.The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the alpha2,6(SAalpha2,6Gal) linkage, while equine viruses favor SAalpha2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] and N-glycolylneuraminic acid [NeuGc]) among different animal...
den Boon JA, Snijder EJ, Chirnside ED, de Vries AA, Horzinek MC, Spaan WJ.The nucleotide sequence of the genome of equine arteritis virus (EAV) was determined from a set of overlapping cDNA clones and was found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed from six 3'-coterminal subgenomic mRNAs, which are transcribed from the 3'-terminal quarter of the viral genome. A number of these ORFs are predicted to encode structural EAV proteins. The organization and expression of the 3' part of the EAV genome are remarkably similar to those of coronaviruses and toroviruses. The 5'-terminal three-quarters of the genome contain the putative EAV p...
Plowright RK, Foley P, Field HE, Dobson AP, Foley JE, Eby P, Daszak P.Anthropogenic environmental change is often implicated in the emergence of new zoonoses from wildlife; however, there is little mechanistic understanding of these causal links. Here, we examine the transmission dynamics of an emerging zoonotic paramyxovirus, Hendra virus (HeV), in its endemic host, Australian Pteropus bats (fruit bats or flying foxes). HeV is a biosecurity level 4 (BSL-4) pathogen, with a high case-fatality rate in humans and horses. With models parametrized from field and laboratory data, we explore a set of probable contributory mechanisms that explain the spatial and tempor...
Quinlivan M, Zamarin D, Garcu00eda-Sastre A, Cullinane A, Chambers T, Palese P.Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, w...
Puffer BA, Parent LJ, Wills JW, Montelaro RC.We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences con...
In the last 30 years several cases of West Nile (WN) virus infection were reported in horses and humans in Europe and in the Mediterranean Basin. Most of them were determined by strains of the Lineage 1 included in the European Mediterranean/Kenyan cluster. Strains of this cluster are characterised by a moderate pathogenicity for horses and humans and limited or no pathogenicity for birds. In recent years, however, WN cases determined by strains grouped in the Israeli/American cluster of Lineage 1 or in the lineage 2 have been reported in Hungary and Austria. The role of migrating birds in int...
Zeller HG, Schuffenecker I.West Nile (WN) virus is a mosquito-transmitted flavivirus. It is widely distributed in Africa, the Middle East, Asia, and southern Europe and was recently introduced to North America. Birds are involved in the cycle of transmission as amplifying hosts. Humans and horses are considered accidental dead-end hosts. WN fever was initially considered a minor arbovirosis, usually inducing a nonsymptomatic or a mild flu-like illness in humans, but some cases of encephalitis associated with fatalities were reported in Israel in the 1950s. After two silent decades, several human and equine outbreaks of ...
Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA, Mishra N, Wagner J, Tokarz R, Cullen JM, Iadarola MJ, Rice CM, Lipkin WI, Kapoor A.Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest p...
Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS.Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and ...
Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ.A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial e...
Selvey LA, Wells RM, McCormack JG, Ansford AJ, Murray K, Rogers RJ, Lavercombe PS, Selleck P, Sheridan JW.To describe the clinical and epidemiological features of an outbreak of a viral infection affecting humans and horses. Methods: Stables in Hendra, a suburb of Brisbane. Methods: Affected horses and humans, and at-risk human contacts. Results: A pregnant mare died two days after arrival from a paddock elsewhere in Brisbane. Eight to 11 days later, illness (depression, anorexia, fever, dyspnoea, ataxia, tachycardia, tachypnoea and nasal discharge) was reported among 17 other horses from the same or an adjoining stable. Fourteen horses died or were put down. Five and six days after the index mare...
Weaver SC, Salas R, Rico-Hesse R, Ludwig GV, Oberste MS, Boshell J, Tesh RB.Venezuelan equine encephalomyelitis (VEE) virus has caused periodic epidemics among human beings and equines in Latin America from the 1920s to the early 1970s. The first major outbreak since 1973 occurred in Venezuela and Colombia during 1995, and involved an estimated 75,000 to 100,000 people. We report an epidemiological and virological investigation of this epidemic. Methods: Virus isolates were made in cell culture from human serum, human throat swabs, and brain tissue from aborted and stillborn human fetuses, as well as from horse brain tissue and pooled mosquito collections. Human sera ...
MacDonald GH, Johnston RE.The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which mi...
van Dinten LC, den Boon JA, Wassenaar AL, Spaan WJ, Snijder EJ.Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a discontinuous transcription mechanism to generate a nested set of six subgenomic mRNAs from which its structural genes are expressed. A stable bacterial plasmid (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was constructed. After removal of a single point mutation in the replicase gene, RNA transcripts generated in vitro from pEAV030 were shown to be infectious upon electroporation into BHK-21 cells. A genetic marker mutation was introduced at the cDNA level and recovered from the genome of the pro...
Saenz RA, Quinlivan M, Elton D, Macrae S, Blunden AS, Mumford JA, Daly JM, Digard P, Cullinane A, Grenfell BT, McCauley JW, Wood JL, Gog JR.A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore...
O'Sullivan JD, Allworth AM, Paterson DL, Snow TM, Boots R, Gleeson LJ, Gould AR, Hyatt AD, Bradfield J.In September, 1994, an outbreak of severe respiratory disease affected 18 horses, their trainer, and a stablehand in Queensland, Australia. Fourteen horses and one human being died. A novel virus was isolated from those affected and named equine morbillivirus (EMV). We report a case of encephalitis caused by this virus. Results: A 35-year-old man from Queensland had a brief aseptic meningitic illness in August, 1994, shortly after caring for two horses that died from EMV infection and then assisting at their necropsies. He then suffered severe encephalitis 13 months later, characterised by unc...
de Vries AA, Chirnside ED, Horzinek MC, Rottier PJ.We have recently shown that the genome of equine arteritis virus (EAV) contains seven open reading frames (ORFs). We now present data on the structural proteins of EAV and the assignment of their respective genes. Virions are composed of a 14-kDa nucleocapsid protein (N) and three membrane proteins designated M, GS, and GL. M is an unglycosylated protein of 16 kDa, and GS and GL are N-glycosylated proteins of 25 and 30 to 42 kDa, respectively. The broad size distribution of GL results from heterogeneous N-acetyllactosamine addition since it is susceptible to digestion by endo-beta-galactosidas...
Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW.Nucleotide sequence analysis of cDNA clones covering the entire genomes of Trinidad donkey (TRD) Venezuelan equine encephalitis (VEE) virus and its vaccine derivative, TC-83, has revealed 11 differences between the genomes of TC-83 virus and its parent. One nucleotide substitution and a single nucleotide deletion occurred in the 5'- and 3'-noncoding regions of the TC-83 genome, respectively. The deduced amino acid sequences of the nonstructural polypeptides of the two viruses differed only in a conservative Ser(TRD) to Thr(TC-83) substitution in nonstructural protein (nsP) three at amino acid ...
Williamson MM, Hooper PT, Selleck PW, Gleeson LJ, Daniels PW, Westbury HA, Murray PK.To determine the infectivity and transmissibility of Hendra virus (HeV). Methods: A disease transmission study using fruit bats, horses and cats. Methods: Eight grey-headed fruit bats (Pteropus poliocephalus) were inoculated and housed in contact with three uninfected bats and two uninfected horses. In a second experiment, four horses were inoculated by subcutaneous injection and intranasal inoculation and housed in contact with three uninfected horses and six uninfected cats. In a third experiment, 12 cats were inoculated and housed in contact with three uninfected horses. Two surviving horse...
Ching PK, de los Reyes VC, Sucaldito MN, Tayag E, Columna-Vingno AB, Malbas FF, Bolo GC, Sejvar JJ, Eagles D, Playford G, Dueger E, Kaku Y....During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.
van Kasteren PB, Bailey-Elkin BA, James TW, Ninaber DK, Beugeling C, Khajehpour M, Snijder EJ, Mark BL, Kikkert M.Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cell...
Komar N, Clark GG.West Nile virus (Flavivirus: Flaviviridae; WNV) has spread rapidly throughout the Caribbean Basin since its initial detection there in 2001. This report summarizes our current knowledge of WNV transmission in tropical America. Methods: We reviewed the published literature and consulted with key public health officials to obtain unpublished data. Results: West Nile virus infections first appeared in human residents of the Cayman Islands and the Florida Keys in 2001, and in apparently healthy Jamaican birds sampled early in 2002. Serologic evidence of WNV infection in 2002 was detected in horses...
Wang LF, Yu M, Hansson E, Pritchard LI, Shiell B, Michalski WP, Eaton BT.An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. W...
Maclachlan NJ, Guthrie AJ.Arthropod-transmitted viruses (Arboviruses) are important causes of disease in humans and animals, and it is proposed that climate change will increase the distribution and severity of arboviral diseases. Orbiviruses are the cause of important and apparently emerging arboviral diseases of livestock, including bluetongue virus (BTV), African horse sickness virus (AHSV), equine encephalosis virus (EEV), and epizootic hemorrhagic disease virus (EHDV) that are all transmitted by haematophagous Culicoides insects. Recent changes in the global distribution and nature of BTV infection have been espec...
Snijder EJ, Wassenaar AL, Spaan WJ.To study the proteolytic processing of the equine arteritis virus (EAV) replicase open reading frame 1a (ORF1a) protein, specific antisera were raised in rabbits, with six synthetic peptides and a bacterial fusion protein as antigens. The processing of the EAV ORF1a product in infected cells was analyzed with Western blot (immunoblot) and immunoprecipitation techniques. Additional information was obtained from transient expression of ORF1a cDNA constructs. The 187-kDa ORF1a protein was found to be subject to at least five proteolytic cleavages. The processing scheme, which covers the entire OR...
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