Biomedical subjects

John D Neill

Publications and source records attributed to John D Neill.

17 recordsLinked to original sources

PubMed2006

Control of antigen mass transfer via capture substrate rotation: an absolute method for the determination of viral pathogen concentration and reduction of heterogeneous immunoassay incubation times.

Immunosorbent assays are commonly employed as diagnostic tests in human healthcare, veterinary medicine and bioterrorism prevention. These assays, however, often require long incubation times, limiting sample throughput. As an approach to overcome this weakness, this paper examines the use of rotating capture substrates to increase the flux of antigen to the surface, thereby reducing the incubation time. To assess the capability of this approach, porcine parvovirus (PPV) was selectively extracted from solution by systematically varying the rotation rate of a gold substrate modified with a layer of anti-PPV monoclonal antibodies. The captured PPV were then directly imaged and quantified by atomic force microscopy. The benefits of substrate rotation are demonstrated by comparing an assay performed under stagnant conditions to one carried out with substrate rotation at 800 rpm, both for 10 min incubations at 25 degrees C. The use of rotation lowered the limit of detection to 3.4x10(4)TCID50/mL (approximately 80 fM) from 3.2x10(5)TCID50/mL (approximately 800 fM) under stagnant conditions. Results are also presented that show this strategy can be used: (1) to determine antigen concentrations without standards and (2) to establish the numerical relationship between quantal concentration units (e.g., 50% tissue culture infective dose (TCID50)) and quantitative concentration units (e.g., viruses/mL) The potential to broadly apply this technique to heterogeneous immunoassays is also briefly discussed.

Antibodies, Monoclonal↗

PubMed2006

X-ray structure of a native calicivirus: structural insights into antigenic diversity and host specificity.

Caliciviruses, grouped into four genera, are important human and veterinary pathogens with a potential for zoonosis. In these viruses, capsid-related functions such as assembly, antigenicity, and receptor interactions are predominantly encoded in a single protein that forms an icosahedral capsid. Understanding of the immunologic functions and pathogenesis of human caliciviruses in the Norovirus and Sapovirus genera is hampered by the lack of a cell culture system or animal models. Much of our understanding of these viruses, including the structure, has depended on recombinant capsids. Here we report the atomic structure of a native calicivirus from the Vesivirus genus that exhibits a broad host range possibly including humans and map immunological function onto a calicivirus structure. The vesivirus structure, despite a similar architectural design as seen in the recombinant norovirus capsid, exhibits novel features and indicates how the unique modular organization of the capsid protein with interdomain flexibility, similar to an antibody structure with a hinge and an elbow, integrates capsid-related functions and facilitates strain diversity in caliciviruses. The internally located N-terminal arm participates in a novel network of interactions through domain swapping to assist the assembly of the shell domain into an icosahedral scaffold, from which the protruding domain emanates. Neutralization epitopes localize to three hypervariable loops in the distal portion of the protruding domain surrounding a region that exhibits host-specific conservation. These observations suggest a mechanism for antigenic diversity and host specificity in caliciviruses and provide a structural framework for vaccine development.

Amino Acid Sequence↗

PubMed2006

Global gene expression profiling of Bovine immature B cells using serial analysis of gene expression.

The Peyer's patches of the small intestine are important sites of antigen processing. The follicles of the Peyer's patches receive the antigen transported by the M cells at the mucosal surface and then play a major role in development of both protective humoral and mucosal immune responses. Serial analysis of gene expression (SAGE) was employed to derive the global gene expression profile of B lymphocytes isolated from the IPPF. Analysis of the SAGE data revealed the identity of genes and the level to which they are expressed by IPPF B lymphocytes. This analysis indicated that they were metabolically active and that the transcripts encoding proteins necessary for a response to antigen presentation were expressed. These transcripts included the B cell receptor components CD76a and b (Ig-alpha and Ig-beta) and accessory c-Src family kinases Lyn and Blk. Furthermore, many of the positive and negative regulators, and accessory proteins that are necessary for B cell antigen receptor signaling were identified. Also present were transcripts encoding interleukins and their cognate receptors. Overall, this SAGE analysis yielded a global picture of gene expression in IPPF B lymphocytes and provides a starting point for the comparison of gene expression in further functional studies.

Animals↗

PubMed2005

Multiple outbreaks of severe acute BVDV in North America occurring between 1993 and 1995 linked to the same BVDV2 strain.

The first reported outbreak of bovine viral diarrhea (BVD) in 1946 described a transmissible acute disease characterized by severe leukopenia, high fever, gastrointestinal erosions and hemorrhages. However, in the ensuing years, the most commonly observed acute form of BVD was clinically mild. There was limited viral shed and spread following these acute infections. This led to the assumptions that acute infections with BVD viruses (BVDV) were clinically unimportant, spread of the virus within a group was always due to the presence of a persistently infected animal and transmission between healthy immunocompetent cattle was insignificant. These assumptions were challenged when outbreaks of severe acute BVDV were observed in North America starting in the late 1980s. This study demonstrates that widespread outbreaks of severe acute BVD observed in 1993 in North America can be traced to a single strain of BVDV that apparently spread explosively following acute infection. These findings are notable in that they draw into question management of acute BVD infection, design of studies examining virulence and nomenclature used to identify strains for GenBank submission.

Acute Disease↗

PubMed2005

Lymphocytopathogenic activity in vitro correlates with high virulence in vivo for BVDV type 2 strains: Criteria for a third biotype of BVDV.

Two biotypes of bovine viral diarrhea viruses (BVDV), cytopathic (cp) and noncytopathic (ncp), are recognized based on their activity in cultured epithelial cells. Biotype does not correlate to virulence in acute infections as BVDV strains associated with severe acute BVD outbreaks are all noncytopathic based on their growth characteristics in cultured epithelial cells. Previous studies have shown that acute infections with highly virulent BVDV result in depletion of cells in lymphoid tissues. In this study, flow cytometry demonstrated that infection with a highly virulent BVDV strain was associated with a pronounced reduction in circulating white blood cells (WBC) and increased numbers of apoptotic and necrotic circulating WBC in vivo. Infection with low virulence BVDV did not result in a significant increase in death of circulating WBC. Thus, there appeared to be a correlation between depletion of circulating WBC and virulence. To study the interaction of BVDV strains with lymphoid cells in the laboratory, we developed an in vitro model that used a bovine lymphoid cell line (BL-3 cells). Using this model, it was found that while BVDV strains are segregated into two biotypes based on their activity in cultured epithelial cells, they may be segregated into three biotypes based on their activity in cultured lymphoid cells. These three biotypes are noncytopathogenic (no obvious effects on the viability of either cultured epithelial or lymphoid cells), cytopathogenic (cytopathic effect and cell death in both cultured epithelial and lymphoid cells within 48 h of infection) and lymphocytopathogenic (no effect on cultured epithelial cells, however, cell death in cultured lymphoid cells is observed within 5 days of infection). The proposed lymphocytopathic biotype correlates with high virulence in acute infections in vivo. Cell death caused by the lymphocytopathogenic biotype was not associated with changes typically seen with cytopathic viruses grown in cultured epithelial cells (e.g. changes in processing of the NS2/3 protein observed within 24h post infection, crenation and breakdown of cell integrity within the first 48 h post infection). These data suggest that the cytopathic effect induced in cultured lymphoid cells by a ncp highly virulent BVDV strain may occur by a different mechanism than the cytopathic effect induced by cp BVDV strains.

Animals↗

PubMed2005

Low-level detection of viral pathogens by a surface-enhanced Raman scattering based immunoassay.

The need for rapid, highly sensitive, and versatile diagnostic tests for viral pathogens spans from human and veterinary medicine to bioterrorism prevention. As an approach to meet these demands, a diagnostic test employing monoclonal antibodies (mAbs) for the selective extraction of viral pathogens from a sample in a chip-scale, sandwich immunoassay format has been developed using surface-enhanced Raman scattering (SERS) as a readout method. The strengths of SERS-based detection include its inherent high sensitivity and facility for multiplexing. The capability of this approach is demonstrated by the capture of feline calicivirus (FCV) from cell culture media that is exposed to a gold substrate modified with a covalently immobilized layer of anti-FCV mAbs. The surface-bound FCVs are subsequently coupled with an extrinsic Raman label (ERL) for identification and quantification. The ERLs consist of 60-nm gold nanoparticles coated first with a layer of Raman reporter molecules and then a layer of mAbs. The Raman reporter molecule is strategically designed to chemisorb as a thiolate adlayer on the gold nanoparticle, to provide a strong and unique spectral signature, and to covalently link a layer of mAbs to the gold nanoparticle. The last feature provides a means to selectively tag substrate-bound FCV. This paper describes the development of the assay, which uses cell culture media as a sample matrix and has a linear dynamic range of 1 x 10(6)-2.5 x 10(8) viruses/mL and a limit of detection of 1 x 10(6) viruses/mL. These results reflect the findings from a detailed series of investigations on the effects of several experimental parameters (e.g., salt concentration, ERL binding buffer, and sample agitation), all of which were aimed at minimizing nonspecific binding and maximizing FCV binding efficiency. The performance of the assay is correlated with the number of captured FCV, determined by atomic force microscopy, as a means of method validation.

Buffers↗

PubMed2004

Induction of T lymphocytes specific for bovine viral diarrhea virus in calves with maternal antibody.

Passive antibody to bovine viral diarrhea virus (BVDV) acquired through colostrum intake may interfere with the development of a protective immune response by calves to this virus. The objective of this study was to determine if calves, with a high level of maternal antibody to bovine viral diarrhea virus (BVDV), develop CD4(+), CD8(+), or gammadelta T lymphocyte responses to BVDV in the absence of a measurable humoral immune response. Colostrum or milk replacer fed calves were challenged with virulent BVDV at 2-5 weeks of age and/or after maternal antibody had waned. Calves exposed to BVDV while passive antibody levels were high did not mount a measurable humoral immune response to BVDV. However, compared to nonexposed animals, these animals had CD4(+), CD8(+), and gammadelta T lymphocytes that were activated by BVDV after exposure to in vitro BVDV. The production of IFNgamma by lymphocytes after in vitro BVDV exposure was also much greater in lymphocytes from calves exposed to BVDV in the presence of maternal antibody compared to the nonexposed calves. These data indicate that calves exposed to BVDV while maternal antibody levels are high can develop antigen specific CD4(+), CD8(+), and gammadelta T lymphocytes in the absence of an active antibody response. A manuscript presented separately demonstrates that the calves with T lymphocytes specific for BVDV in this study were also protected from virulent BVDV genotype 2 challenge after maternal antibody became undetectable.

Animals↗

PubMed2004

Inter- and intragenus structural variations in caliciviruses and their functional implications.

The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses with a documented potential for zoonoses. To investigate inter- and intragenus structural variations and to provide a better understanding of the structural basis of host specificity and strain diversity, we performed structural studies of the recombinant capsid of Grimsby virus, the recombinant capsid of Parkville virus, and San Miguel sea lion virus serotype 4 (SMSV4), which are representative of the genera Norovirus (genogroup 2), Sapovirus, and Vesivirus, respectively. A comparative analysis of these structures was performed with that of the recombinant capsid of Norwalk virus, a prototype member of Norovirus genogroup 1. Although these capsids share a common architectural framework of 90 dimers of the capsid protein arranged on a T=3 icosahedral lattice with a modular domain organization of the subunit consisting of a shell (S) domain and a protrusion (P) domain, they exhibit distinct differences. The distally located P2 subdomain of P shows the most prominent differences both in shape and in size, in accordance with the observed sequence variability. Another major difference is in the relative orientation between the S and P domains, particularly between those of noroviruses and other caliciviruses. Despite being a human pathogen, the Parkville virus capsid shows more structural similarity to SMSV4, an animal calicivirus, suggesting a closer relationship between sapoviruses and animal caliciviruses. These comparative structural studies of caliciviruses provide a functional rationale for the unique modular domain organization of the capsid protein with an embedded flexibility reminiscent of an antibody structure. The highly conserved S domain functions to provide an icosahedral scaffold; the hypervariable P2 subdomain may function as a replaceable module to confer host specificity and strain diversity; and the P1 subdomain, located between S and P2, provides additional fine-tuning to position the P2 subdomain.

Amino Acid Sequence↗

PubMed2004

Distribution of viral antigen and tissue lesions in persistent and acute infection with the homologous strain of noncytopathic bovine viral diarrhea virus.

Viral distribution and lesions were compared between calves born with persistent infection (PI) and calves acutely infected with the same bovine viral diarrhea virus (BVDV) isolate. Two PI calves from 1 dairy herd were necropsied. The PI viruses from these calves were isolated, characterized by sequencing, and found to be identical. This virus strain, designated BVDV2-RS886, was characterized as a noncytopathic (ncp) type 2 BVDV. To establish acute infections, BVDV2-RS886 was used to inoculate clinically healthy, seronegative calves which were 3 weeks to 3 months old. Nine calves received 10(6)-10(7) tissue culture infective dose of BVDV2-RS886 intranasally. Four additional age-matched animals served as noninfected controls. Infected calves were necropsied at 3, 6, 9, or 13 days postinoculation (dpi). Viral antigen was detected by immunohistochemistry in frozen sections, and lesions were evaluated in hematoxylin eosin-stained paraplast sections. In the PI calves, a wide distribution of viral antigen was found in all tissues and was not associated with lesions. In the acutely infected calves, viral antigen was widespread in lymphoid tissues at 6 dpi but had been mostly eliminated at 9 and 13 dpi. Depletion of lymphoid tissues was seen at 6, 9, and 13 dpi and repopulation at 9 and 13 dpi. In 1 of the calves at 13 dpi, severe arteritis was present in lymph nodes and myocardium. This comparison shows that an ncp BVDV strain that causes no lesions in PI animals is able to induce marked depletion of lymphoid tissues in calves with acute infection. Therefore, the failure to eliminate PI cattle from a herd causes problems not only in pregnant cattle but may also affect other age groups.

Animals↗

PubMed2003

Gene expression changes in MDBK cells infected with genotype 2 bovine viral diarrhoea virus.

Bovine viral diarrhoea viruses (BVDVs) are ubiquitous viral pathogens of cattle. These viruses exist as one of two biotypes, cytopathic and noncytopathic, based on the ability to induce cytopathic effect in cell culture. The noncytopathic biotypes are able to establish inapparent, persistent infections in both cell culture and in bovine foetuses of less than 150 days gestation. Interactions with the host cell and the mechanism by which viral tolerance is established are unknown. To examine the changes in gene expression that occur following infection of host cells with BVDV, serial analysis of gene expression (SAGE), a global gene expression technology was used. SAGE allows quantitation of virtually every transcript in a cell type without prior sequence information. Transcript expression levels and identities are determined by sequencing libraries composed of concatamers of 14 base DNA fragments (tags) derived from the 3'-end of each cellular mRNA transcript. Comparison of data obtained from uninfected and BVDV genotype 2-infected cell libraries revealed changes in gene expression associated with distinct biochemical pathways or functions. Isotypes of both alpha- and beta-tubulins were down-regulated, indicating possible dysfunction in cell division and other functions where microtubules play a major role. Expression of genes encoding proteins involved in energy metabolism were expressed at essentially equivalent levels in both infected and uninfected cells. Genes encoding proteins involved in protein translation and post-translational modifications, functions necessary for viral replication, were generally up-regulated. These data indicate that following infection with BVDV, changes in gene expression occur that are beneficial for virus replication while having only minor changes in energy metabolism.

Animals↗

PubMed2003

Gene expression changes in BVDV2-infected MDBK cells.

Bovine viral diarrhoea virus (BVDV) is a ubiquitous viral pathogen of cattle. The virus exists as one of two biotypes, cytopathic and non-cytopathic, based on the ability to induce cytopathic effect in cell culture. The non-cytopathic biotypes are able to establish non-apparent, persistent infections in both cell culture and in bovine foetuses of fewer than 150 days gestation. The mechanism by which viral tolerance is established is unknown. To examine the changes in gene expression that occur following infection of host cells with BVDV, serial analysis of gene expression (SAGE), a global gene expression technology was used. SAGE, a sequence-based technology, allows quantification of virtually every transcript in a cell type without prior sequence information. Transcript expression levels and identities are determined by DNA sequencing of libraries composed of 14 base DNA fragments (tags) derived from the 3' end of each cellular mRNA transcript. Comparison of data obtained from non-infected and BVDV2-infected cell libraries revealed a number of changes in gene expression. Many of these transcriptional changes could be placed into distinct biochemical pathways or functions. Both alpha and beta tubulins were downregulated, indicating possible dysfunction in cell division and other functions where microtubules play a major role. Expression of several genes encoding proteins involved in energy metabolism were downregulated, indicating possible decreased ATP synthesis. Genes encoding proteins involved in protein translation and post-translational modifications were generally upregulated. These data indicate that following infection with BVDV, changes in gene expression occur that are beneficial for virus replication while placing the cell at a metabolic disadvantage.

Adenosine Triphosphate↗

PubMed2003

Crystallization and preliminary crystallographic analysis of San Miguel sea lion virus: an animal calicivirus.

The Caliciviridae is a family of nonenveloped, icosahedral, positive-sense single-stranded RNA viruses. This family of viruses consists of both animal and human pathogens. Adapting human caliciviruses to cell culture has not been successful, whereas some animal caliciviruses, including San Miguel sea lion virus, have been successfully propagated in vitro. Here we report the crystallization of San Miguel sea lion virus serotype 4 (SMSV4) and the preliminary X-ray crystallographic analysis of the crystals. SMSV4 have been crystallized using the hanging-drop method. These crystals diffracted to approximately 3A resolution using a synchrotron radiation source. A single crystal under cryo-conditions yielded a complete set of diffraction data. Data processing of the diffraction patterns showed that SMSV crystals belong to I23 space group with cell dimensions a=b=c=457 A. The crystallographic asymmetric unit includes five icosahedral asymmetric units, each consisting of three capsid protein subunits. In the space group I23, given the icosahedral symmetry and the size of the virus particle, the location of the particle is constrained to be at the point where the crystallographic 2- and 3-fold axes intersect. The orientation of the virus particle in the unit cell was ascertained by self-rotation function calculations.

Capsid↗

PubMed2003

Distribution of viral antigen and development of lesions after experimental infection of calves with a BVDV 2 strain of low virulence.

To examine the virus-host interaction in subclinical bovine viral diarrhea virus (BVDV) infections, the spread of a BVDV 2 strain of low virulence to different organs and the development of lesions were investigated. Eight colostrum-deprived, clinically healthy, 2-3-month-old calves were intranasally inoculated with 10(6) tissue culture infective dose of the naturally occurring BVDV 2 strain 28508-5 of low virulence, and 2 served as controls. Two calves each were euthanized at days 3, 6, 9, and 13 postinoculation (pi). Representative tissues were processed for histology and immunohistology. Signs of overt clinical disease were absent. However, a mild temperature elevation at days 7 or 8 pi and a moderate decrease of circulating lymphocytes occurred in all inoculated calves. The BVDV antigen was detected at day 3 pi in several lymphoid tissues. At day 6 pi, BVDV antigen was found widespread in lymphoid tissues and multifocally in intestinal epithelial cells but was associated with no or subtle lesions only. At day 9 pi, much less BVDV antigen was detectable, but there was severe depletion of lymphoid tissues. At day 13 pi, BVDV antigen had been cleared from most lymphoid tissues that were at variable phases of depletion and recovery. In conclusion, the BVDV strain of low virulence spread to lymphoid tissues and intestinal epithelial cells but was rapidly eliminated. Transient depletion of lymphoid tissues was followed by recovery.

Animals↗

PubMed2003

Effect of passive immunity on the development of a protective immune response against bovine viral diarrhea virus in calves.

OBJECTIVE: To determine whether passively acquired antibodies prevent development of a protective immune response to live virus in calves. ANIMALS: 18 calves. PROCEDURES: Calves were caught immediately after birth and tested free of bovine viral diarrhea virus (BVDV) and serum antibodies against BVDV. Within 48 hours, 12 calves were fed colostrum that contained antibodies against BVDV and 6 calves received BVDV antibody free milk replacer. Three milk replacer fed and 6 colostrum fed calves were exposed to virulent BVDV2-1373 at 2 to 5 weeks of life when passively acquired serum antibody titers were high. After serum antibody titers against BVDV had decayed to undetectable concentrations (at 7 to 9 months of age), the 3 remaining milk replacer fed calves, 6 colostrum fed calves previously exposed to BVDV2-1373, and 6 colostrum fed calves that had not been exposed to the virus were inoculated with BVDV2-1373. RESULTS: Passively acquired antibodies prevented clinical disease in inoculated colostrum fed calves at 2 to 5 weeks of life. Serum antibody titers did not increase in these calves following virus inoculation, and serum antibody titers decayed at the same rate as in noninoculated colostrum fed calves. Inoculated colostrum fed calves were still protected from clinical disease after serum antibody titers had decayed to nondetectable concentrations. Same age colostrum fed calves that had not been previously exposed to the virus were not protected. CONCLUSIONS AND CLINICAL RELEVANCE: A protective immune response was mounted in calves with passive immunity, but was not reflected by serum antibodies titers. This finding has implications for evaluating vaccine efficacy and immune status.

Animals↗

PubMed2002

The subgenomic RNA of feline calicivirus is packaged into viral particles during infection.

During infection, feline calicivirus (FCV) produces an abundant subgenomic RNA of 2.4 kb that is the major template for translation of the single capsid protein. Feline cells infected with FCV (CFI/68 strain) at a high multiplicity of infection produced a population of lower density (ld) viral particles with a density of 1.35 g/cc as compared to the 1.39 g/cc density of the wild-type virus particle. The RNA isolated from the ld particles was 2.4 kb in size, the same as that of the intracellular subgenomic transcript that encodes the single capsid protein of the virus. Primer extension analysis revealed that the 5' end of the RNA from the ld particles mapped to the same genomic location as the intracellular 2.4 kb RNA. RNA protection of the ld RNA using a FCV 4.2 kb minus strand cDNA containing 1984 bases of capsid protein coding sequences, protected an RNA fragment of approximately 2000 bases. The data presented here demonstrates that the ld particles contains the FCV subgenomic RNA and not a genomic RNA containing rearrangements or deletions.

Animals↗

PubMed2002

Evaluation of the reverse transcription-polymerase chain reaction/probe test of serum samples and immunohistochemistry of skin sections for detection of acute bovine viral diarrhea infections.

Bovine viral diarrhea viruses (BVDV) cause both acute and persistent infections. While diagnostic tests have been designed to detect animals persistently infected (PI) with BVDV, the reliability of these tests in detecting acute BVDV infections is not known. It is also possible that acute BVDV infections may be confused with persistent infections in surveys for PI animals. In this study, 2 tests presently in use in diagnostic laboratories to test for PI animals, polymerase chain reaction amplification followed by probe hybridization (RT-PCR/probe) of serum samples and immunohistochemical detection of viral antigen in skin biopsies (IHC), were evaluated for their ability to detect acute BVDV infections. Sixteen colostrum-deprived, BVDV-free, and BVDV-antibody-free calves were infected with 6 different BVDV strains. Clinical signs, seroconversion, and virus isolation indicated that inoculated animals did replicate virus. Virus could be detected in 19% (3/16) of acutely infected animals by the RT-PCR/probe technique. No acutely infected animals were positive by IHC.

Acute Disease↗

PubMed2002

Distribution of viral antigen and development of lesions after experimental infection with highly virulent bovine viral diarrhea virus type 2 in calves.

OBJECTIVE: To correlate tissue distribution with development of lesions after experimental infection with a virulent strain of noncytopathic bovine viral diarrhea virus (BVDV) type 2 in calves. ANIMALS: Ten 14-day-old and two 2-month-old colostrum-deprived calves. PROCEDURE: Calves were intranasally inoculated with BVDV type-2 strain 1373 from an outbreak of clinically severe bovine viral diarrhea (BVD). Two 14-day-old calves served as noninfected controls. Two calves each were euthanatized on postinoculation days 3, 6, and 12, and 1 each on days 8, 9, 13, and 14. Tissues were collected for immunohistologic and histologic examination. RESULTS: Inoculated calves developed nonspecific clinical signs characterized by high fever and decreased numbers of leukocytes and thrombocytes. Viral antigen was detected focally in lymphoid tissues on day 3. On days 6, 8, 9, 12, and 14, viral antigen became increasingly widespread throughout organs and tissues. Viral antigen in lymphoid tissues was associated with severe depletion of all compartments. Lesions in other tissues were not well correlated with distribution of viral antigen. Depletion of lymphoid tissues was observed in a calf on day 13, but viral antigen had been cleared from most tissues and was detected in vascular walls only. CONCLUSIONS AND CLINICAL RELEVANCE: Infection with a virulent BVDV strain resulted in wide dissemination of viral antigen in host tissues. Severe lymphoid depletion developed in lymphoid tissues, whereas viral antigen was generally not associated with lesions in other tissues. Findings suggest that development of lesions in acute BVD is not solely a function of viral replication and is also attributable to host reaction to infection.

Animals↗