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N J MacLachlan

Publications and source records attributed to N J MacLachlan.

At least 19 recordsLinked to original sources
PubMed2004

Pathologic, immunohistochemical, and electron microscopic findings in naturally occurring virulent systemic feline calicivirus infection in cats.

Infection with feline calicivirus (FCV) is a common cause of upper respiratory and oral disease in cats. FCV infection is rarely fatal, however, virulent, systemic strains of FCV (VS-FCV) that cause alopecia, cutaneous ulcers, subcutaneous edema, and high mortality in affected cats have recently been described. Seven cats with natural VS-FCV infection all had subcutaneous edema and ulceration of the oral cavity, with variable ulceration of the pinnae, pawpads, nares, and skin. Other lesions that were present in some affected cats included bronchointerstitial pneumonia, and pancreatic, hepatic, and splenic necrosis. Viral antigen was present within endothelial and epithelial cells in affected tissues as determined by immunohistochemical staining with a monoclonal antibody to FCV. Mature intranuclear and intracytoplasmic virions in necrotic epithelial cells were identified by transmission electron microscopy. VS-FCV infection causes epithelial cell cytolysis and systemic vascular compromise in susceptible cats, leading to cutaneous ulceration, severe edema, and high mortality.

Animals↗
PubMed2003

Lateral transmission of equine arteritis virus among Lipizzaner stallions in South Africa.

REASONS FOR PERFORMING STUDY: A serological study conducted in 1995 revealed that 7 stallions at the Lipizzaner Centre, Gauteng, South Africa, were seropositive for antibody to equine arteritis virus (EAV). A Lipizzaner stallion imported into South Africa from Yugoslavia in 1981 had previously (1988) been confirmed to be an EAV carrier. Despite being placed under life-long breeding quarantine, EAV had been transmitted between stallions at the Lipizzaner Centre. OBJECTIVES: To investigate the phylogenetic relationships between the strain of EAV shed in the semen of the original carrier stallion and strains recovered from the semen of 5 other stallions; and to investigate the means whereby lateral transmission of EAV occurred among 7 in-contact, nonbreeding stallions at the Centre. METHODS: EAV was isolated from semen collected from the seropositive stallions using RK-13 cells. Viral RNA was reverse transcribed and amplified by polymerase chain reaction using ORF 5-specific primers, subjected to sequence and phylogenetic analysis. RESULTS: Phylogenetic analysis of strains of EAV recovered from the semen of 6 persistently infected stallions confirmed that all viruses were closely related and probably derived from a common ancestor, i.e. the stallion imported from Yugoslavia. Lateral transmission subsequently occurred among 7 in-contact, nonbreeding stallions at the Centre. It is speculated that these stallions may have been exposed to virus from bedding or fomites contaminated with semen. CONCLUSIONS: These data confirm that lateral transmission of EAV can occur from shedding stallions to susceptible, in-contact horses, including other stallions, which may become persistently infected with the virus. POTENTIAL RELEVANCE: The findings are consistent with lateral spread of a single, unique strain of EAV among a group; and suggest that transmission of EAV may be initiated by infection of one or more stallions with virus on bedding or other fomites contaminated with EAV- infected semen.

Animals↗
PubMed2003

West Nile virus infection of Thoroughbred horses in South Africa (2000-2001).

REASONS FOR PERFORMING STUDY: West Nile virus (WNV) infection is endemic in southern Africa. With the recent emergence of WNV infection of horses in Europe and the USA the present study was performed to estimate the risk of seroconversion to WNV in a cohort of 488 young Thoroughbred (TB) horses. OBJECTIVES: To estimate the risk of seroconversion to WNV among a cohort of South African TB yearlings sold at the 2001 National Yearling Sales (NYS) and to determine whether the risk varied geographically. Two horses were also infected with a recent South African isolate of WNV to evaluate its virulence in horses. METHODS: Serum samples were collected from the cohort of 488 TB yearlings at the 2001 NYS. Serum samples that were collected from the same horses at the time that they were identified were sourced from our serum bank. Sera from 243 of the dams that were collected at the time that the foals were identified were also sourced from our serum bank. These sera were subjected to serum neutralisation (SN) tests for antibody to WNV. RESULTS: Approximately 11% of yearlings seroconverted to WNV on paired serum samples collected from each animal approximately 12 months apart. Studfarms with WNV-seropositive yearlings were widely distributed throughout South Africa and SN tests on sera from their dams indicated that exposure to WNV was even more prevalent (75%) in this population. Neurological disease was not described in any of the horses included in this study and 2 horses inoculated with a recent lineage 2 South African isolate of WNV showed no clinical signs of disease after infection and virus was not detected in their blood. CONCLUSIONS: Infection of horses with WNV is common in South Africa, but infection is not associated with neurological disease. POTENTIAL RELEVANCE: In contrast to recent reports from Europe, North Africa, Asia and North America, the results of our field and experimental studies indicated that exposure of horses to the endemic southern African strains of WNV was not associated with neurological disease.

Animals↗
PubMed2002

Duration of viraemia infectious to Culicoides sonorensis in bluetongue virus-infected cattle and sheep.

The duration of viraemia infectious to Culicoides sonorensis (C. sonorensis) was evaluated in bluetongue virus (BTV)-infected sheep and cattle by feeding laboratory-reared C. sonorensis directly on the skin of ruminants that previously were infected with BTV by insect inoculation. The intervals after infection when infectious BTV and BTV nucleic acids were present in the blood of infected cattle and sheep, respectively, were determined by virus isolation and reverse transcriptase (RT)-nested polymerase chain reaction (PCR) assays. The presence of BTV in vector insects that fed on the BTV-infected cattle and sheep at 7, 21, and 49 days post-infection (p.i.) was also determined by virus isolation and RT-PCR assays. BTV was isolated from the blood of infected cattle for up to 49 days p.i., whereas it was not isolated from the BTV-infected sheep after 11 days p.i. In contrast, BTV nucleic acids were detected in the blood of infected ruminants for 111-222 days p.i. The maximal duration of viraemia that was infectious to C. sonorensis was 21 days p.i. of both cattle and sheep and, with the notable exception of one sheep at 21 days p.i., only ruminants whose blood contained BTV as determined by virus isolation were able to infect C. sonorensis after oral feeding. Data from this and previous studies indicates that viraemia is transient in BTV-infected ruminants, and that the RT-nested PCR assay provides a very sensitive and conservative test for the screening of cattle and sheep for the presence of BTV.

Animals↗
PubMed2001

Seroprevalence of antibodies against equine arteritis virus in horses residing in the United States and imported horses.

OBJECTIVE: To compare seroprevalence of antibodies against equine arteritis virus (EAV) in horses residing in the United States with that of imported horses. DESIGN: Serologic survey. SAMPLE POPULATION: Serum samples from 364 horses on 44 equine operations in California and 226 horses imported from various countries. PROCEDURE: Serum samples were collected from each imported horse and from up to 20 horses on each operation. For resident horses, the number of sampled horses on each operation was determined on the basis of the number of horses on the operation. Samples were tested for antibodies against EAV by use of a serum neutralization test. RESULTS: 1.9% of resident horses and 18.6% of imported horses were seropositive to EAV, including 16.1% of imported stallions. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that the EAV seroprevalence of horses residing in California is considerably lower than that of imported horses, including imported stallions.

Animals↗
PubMed2001

Characterization of equine E-selectin.

Expression of E-selectin on activated endothelium is a critical initial step that leads to extravasation of leucocytes during inflammation, yet E-selectin is largely uncharacterized in several animal species including the horse. We have sequenced and compared E-selectin genes derived from activated cultures of purified equine (horse), cervid (black-tailed deer) and ovine (sheep) pulmonary artery endothelial cells (ECs). Phylogenetic and amino acid sequence comparisons indicate that bovine, cervid and ovine E-selectin are similar, whereas human and equine E-selectin are more closely related to each other than to the ruminant molecules. Human E- and P-selectin-specific monoclonal antibodies that also recognize equine E-selectin were identified and used to characterize its expression. Expression of E-selectin was more readily induced by lipopolysaccharide treatment in equine ECs than in human ECs and supported adhesion and activation of neutrophils, consistent with the extreme sensitivity of horses to endotoxaemia and septic shock.

Amino Acid Sequence↗
PubMed2001

Occurrence of genetic drift and founder effect during quasispecies evolution of the VP2 and NS3/NS3A genes of bluetongue virus upon passage between sheep, cattle, and Culicoides sonorensis.

Bluetongue virus (BTV) is the cause of an insect-transmitted virus infection of ruminants that occurs throughout much of the world. Individual gene segments differ between field strains of BTV; thus, we hypothesized that key viral genes undergo genetic drift during alternating passage of BTV in its ruminant and insect hosts. To test this hypothesis, variation in the consensus sequence and quasispecies heterogeneity of the VP2 and NS3/NS3A genes of a plaque-purified strain of BTV serotype 10 was determined during alternating infection of vector Culicoides sonorensis and a sheep and calf. Consensus sequences were determined after reverse transcriptase-nested PCR amplification of viral RNA directly from ruminant blood and homogenized insects, and quasispecies heterogeneity was determined by the sequencing of clones derived from directly amplified viral RNA. Comparison of these sequences to those of the original BTV inoculum used to initiate the cycle of BTV infection demonstrated, for the first time, that individual BTV gene segments evolve independently of one another by genetic drift in a host-specific fashion, generating quasispecies populations in both ruminant and insect hosts. Furthermore, a unique viral variant was randomly ingested by C. sonorensis insects that fed on a sheep with low-titer viremia, thereby fixing a novel genotype by founder effect. Thus, we conclude that genetic drift and founder effect contribute to diversification of individual gene segments of field strains of BTV.

Animals↗
PubMed2001

Maximal predicted duration of viremia in bluetongue virus-infected cattle.

Central to the development of rational trade policies pertaining to bluetongue virus (BTV) infection is determination of the risk posed by ruminants previously exposed to the virus. Precise determination of the maximal duration of infectious viremia is essential to the development of an appropriate quarantine period prior to movement of animals from BTV-endemic to BTV-free regions. The objective of this study was to predict the duration of detectable viremia in BTV-infected cattle using a probabilistic modeling analysis of existing data. Data on the duration of detectable viremia in cattle were obtained from previously published studies. Data sets were created from a large field study of naturally infected cattle in Australia and from experimental infections of cattle with Australian and US serotypes of BTV. Probability distributions were fitted to the pooled empirical data, and the 3 probability distributions that provided the best fit to the data were the gamma, Weibull, and lognormal probability distributions. These asymmetric probability distributions are often well suited for decay processes, such as the time to termination of detectable viremia. The analyses indicated a > 99% probability of detectable BTV viremia ceasing after < or = 9 weeks of infection in adult cattle and after a slightly longer interval in BTV-infected, colostrum-deprived newborn calves.

Animals↗
PubMed2000

Bluetongue and equine viral arteritis viruses as models of virus-induced fetal injury and abortion.

A number of viruses have the capacity to cross the placenta and infect the fetus to cause, among other potential outcomes, developmental defects (teratogenesis), fetal death and abortion. Bluetongue virus (BTV) infection of fetal ruminants provides an excellent model for the study of virus-induced teratogenesis. This model has shown that only viruses modified by passage in cell culture, such as modified live virus vaccine strains, readily cross the ruminant placenta, and that the timing of fetal infection determines the outcome. Thus, cerebral malformations only occur after fetal infection at critical stages during development and the precise timing of fetal BTV infection determines the severity of the malformation present at birth. Fetal BTV infection also can result in fetal death, followed by abortion or resorption, growth retardation, or no obvious abnormalities, depending on age of the conceptus at infection. Equine arteritis virus (EAV) infection of the equine fetus causes fetal death and abortion but not teratogenesis. These two fetal viral infections are useful not only for the study of teratogenesis and fetal disease, but also to further characterize and compare the complex process that is responsible for normal induction of parturition in ruminants and horses.

Abortion, Veterinary↗
PubMed2000

Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats.

OBJECTIVE: To evaluate serum feline trypsin-like immunoreactivity (fTLI) concentration and results of abdominal ultrasonography, CBC, and serum biochemical analyses for diagnosis of pancreatitis in cats. DESIGN: Prospective study. ANIMALS: 28 cats with clinical signs compatible with pancreatitis. PROCEDURE: Serum fTLI concentrations were determined, and abdominal ultrasonography, CBC, and serum biochemical analyses were performed prior to histologic evaluation of pancreatic, hepatic, and intestinal specimens. On the basis of histologic results, cats were categorized as having a normal pancreas (n = 10), pancreatic fibrosis with ongoing inflammation (9), pancreatic fibrosis without inflammation (4), and acute necrotizing pancreatitis (5). Serum fTLI concentrations and results of CBC, serum biochemical analyses, and histologic evaluation of hepatic and intestinal specimens were compared among groups. RESULTS: Significant differences in serum fTLI concentrations or any hematologic or biochemical variable were not detected among the 4 groups of cats. Median serum fTLI concentrations were 51 micrograms/L (range, 18 to 200 micrograms/L) in cats with a normal pancreas, 32 micrograms/L (range, 12 to > 200 micrograms/L) in cats with pancreatic fibrosis and ongoing inflammation, 124 micrograms/L (range, 36 to > 200 micrograms/L) in cats with pancreatic fibrosis without ongoing inflammation, and 30 micrograms/L (range, 24 to 84 micrograms/L) in cats with acute necrotizing pancreatitis. We detected a high prevalence of concurrent hepatic and intestinal tract disease in cats with pancreatitis. CONCLUSIONS AND CLINICAL RELEVANCE: In cats with clinical signs of pancreatitis, serum fTLI concentration is poorly associated with histopathologic diagnosis.

Acute Disease↗
PubMed2000

Changes in the outer capsid proteins of bluetongue virus serotype ten that abrogate neutralization by monoclonal antibodies.

Six neutralizing monoclonal antibodies (Mabs) and nine neutralization resistant viral variants (escape-mutant viruses (EMVs)) were used to further characterize the neutralization determinants of bluetongue virus serotype 10 (BTV10). The EMVs were produced by sequential passage of a highly cell culture adapted United States prototype strain of BTV10 in the presence of individual neutralizing Mabs. Mabs were characterized by neutralization and immune precipitation assays, and phenotypic properties of EMVs were characterized by neutralization assay. Sequencing of the gene segments encoding outer capsid proteins VP2 and VP5 identified mutations responsible for the altered phenotypic properties exhibited by individual EMVs. Amino acid substitutions in VP2 were responsible for neutralization resistance in most EMVs, whereas an amino acid substitution in VP5, without any change in VP2, was responsible for the neutralization resistance of one EMV. The data confirm that VP2 contains the major neutralization determinants of BTV, and that VP5 also can influence neutralization of the virus. The considerable plasticity of the neutralization determinants of BTV has significant implications for future development of non-replicating vaccines.

Amino Acid Substitution↗
PubMed2000

Expression of the two major envelope proteins of equine arteritis virus as a heterodimer is necessary for induction of neutralizing antibodies in mice immunized with recombinant Venezuelan equine encephalitis virus replicon particles.

RNA replicon particles derived from a vaccine strain of Venezuelan equine encephalitis virus (VEE) were used as a vector for expression of the major envelope proteins (G(L) and M) of equine arteritis virus (EAV), both individually and in heterodimer form (G(L)/M). Open reading frame 5 (ORF5) encodes the G(L) protein, which expresses the known neutralizing determinants of EAV (U. B. R. Balasuriya, J. F. Patton, P. V. Rossitto, P. J. Timoney, W. H. McCollum, and N. J. MacLachlan, Virology 232:114-128, 1997). ORF5 and ORF6 (which encodes the M protein) of EAV were cloned into two different VEE replicon vectors that contained either one or two 26S subgenomic mRNA promoters. These replicon RNAs were packaged into VEE replicon particles by VEE capsid protein and glycoproteins supplied in trans in cells that were coelectroporated with replicon and helper RNAs. The immunogenicity of individual replicon particle preparations (pVR21-G(L), pVR21-M, and pVR100-G(L)/M) in BALB/c mice was determined. All mice developed antibodies against the recombinant proteins with which they were immunized, but only the mice inoculated with replicon particles expressing the G(L)/M heterodimer developed antibodies that neutralize EAV. The data further confirmed that authentic posttranslational modification and conformational maturation of the recombinant G(L) protein occur only in the presence of the M protein and that this interaction is necessary for induction of neutralizing antibodies.

Animals↗
PubMed2000

An epizootic of adenovirus-induced hemorrhagic disease in captive black-tailed deer (Odocoileus hemionus).

Ten fawns and four adult black-tailed deer (Odocoileus hemionus) in a captive herd died as a result of adenovirus-induced hemorrhagic disease. Acute, systemic infections were characterized by hemorrhagic enteropathy, pulmonary edema, and occasional ulceration of the upper alimentary tract. Localized infections were limited to the upper alimentary tract and included stomatitis, pharyngitis, mandibular osteomyelitis, and rumenitis. In deer with acute, systemic infections, a diagnosis was made by histopathology and immunohistochemistry. The serum neutralization test was useful for confirming a diagnosis in animals with prolonged, localized infections. Deer originating from herds with a history of adenovirus infection should not be transferred to other captive herds or released into free-ranging populations because they may serve as carriers of adenovirus.

Adenoviridae↗
PubMed2000

Serologic detection of adenoviral hemorrhagic disease in black-tailed deer in California.

An enzyme-linked immunosorbent assay (ELISA) and a serum neutralization (SN) test were developed to measure serum antibodies against the adenovirus causing hemorrhagic disease in free-ranging and captive experimentally-infected black-tailed deer (Odocoilenus hemionus columbianus) in California (USA). There was a strong (rho = 0.874) and significant (P < 0.0001) correlation between ELISA and SN titers, although the SN assay was more sensitive than the ELISA.

Adenoviridae Infections↗
PubMed1999

The open reading frame 3 of equine arteritis virus encodes an immunogenic glycosylated, integral membrane protein.

Open reading frame 3 (ORF 3) of equine arteritis virus (EAV) is predicted to encode a glycosylated membrane protein (GP3) that is uncharacterized. ORF 3 of the American Type Culture Collection strain of EAV was in vitro transcribed and the encoded GP3 protein was in vitro translated with and without canine microsomal membranes. The GP3 protein was approximately 17 kDa after in vitro translation without canine microsomal membranes whereas the glycosylated form, after translation with microsomal membranes, was a diffuse band of 36-42 kDa, indicating that the GP3 protein is extensively glycosylated. Deglycosylation reduced the GP3 protein to approximately 17 kDa, the same size as that translated without microsomal membranes, indicating that the signal sequence was not cleaved. The EAV GP3 protein was membrane associated and not released as a soluble protein, in marked contrast to the ORF 3-encoded proteins of some other arteriviruses. The GP3 protein was protected from protease digestion in closed membrane vesicles, suggesting that the protein extends into the membrane vesicles and is anchored by the N-terminal signal sequence, a C-terminal hydrophobic domain, or both, but does not span the membrane three times. A GP3 protein lacking the C-terminal transmembrane domain remained membrane associated, indicating that this terminus is not a necessary membrane anchor. Sera from stallions persistently infected with EAV and horses immunized repeatedly with the modified live EAV vaccine contained antibodies specific for the GP3 protein. The data indicate that the GP3 protein is an extensively glycosylated membrane protein that is immunogenic during some EAV infections.

Animals↗
PubMed1999

Identification of seven serotypes of bluetongue virus from the People's Republic of China.

Seven serotypes (1, 2, 3, 4, 12, 15 and 16) of bluetongue virus were isolated from the blood of sheep and cattle in the People's Republic of China between 1986 and 1996. Six of these viruses were isolated in Yunnan province. The sheep from which serotypes 1 and 16 were isolated showed obvious signs of bluetongue disease, whereas the cattle from which serotypes 2, 3, 4, 12 and 15 were isolated were clinically normal. Phylogenetic analyses of these viruses indicate that they are more closely related to one another, and to an Australian strain of serotype 1, than they are to prototype strains of bluetongue virus serotypes 2, 10, 11, 13 and 17 from the USA.

Animals↗