Bradley L. Njaa

The Virulence of 1997 H5N1 Influenza Viruses in the Mouse Model Is Increased by Correcting a Defect in Their NS1 Proteins

ABSTRACT The NS1 protein of human influenza A viruses binds the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a protein required for 3′ end processing of cellular pre-mRNAs, thereby inhibiting production of beta interferon (IFN-β) mRNA. The NS1 proteins of pathogenic 1997 H5N1 viruses contain the CPSF30-binding site but lack the consensus amino acids at positions 103 and 106, F and M, respectively, that are required for the stabilization of CPSF30 binding, resulting in nonoptimal CPSF30 binding in infected cells. Here we have demonstrated that strengthening CPSF30 binding, by changing positions 103 and 106 in the 1997 H5N1 NS1 protein to the consensus amino acids, results in a remarkable 300-fold increase in the lethality of the virus in mice. Unexpectedly, this increase in virulence is not associated with increased lung pathology but rather is characterized by faster systemic spread of the virus, particularly to the brain, where increased replication and severe pathology occur. This increased spread is associated with increased cytokine and chemokine levels in extrapulmonary tissues. We conclude that strengthening CPSF30 binding by the NS1 protein of 1997 H5N1 viruses enhances virulence in mice by increasing the systemic spread of the virus from the lungs, particularly to the brain.

Pseudorabies virus infection in Oklahoma hunting dogs

Pseudorabies is caused by Suid herpesvirus 1, a member of the Alphaherpesvirinae subfamily. Although pigs are the natural host of Pseudorabies virus (PRV), the virus has a broad host range and may cause fatal encephalitis in many species. The United States obtained PRV-free status in 2004 after the virus was eradicated from domestic swineherds, but the virus is still present in feral swine populations. The current report describes PRV infection in 3 dogs that were used to hunt feral swine. The dogs developed clinical signs including facial pruritus with facial abrasions, dyspnea, vomiting, diarrhea, ataxia, muscle stiffness, and death. Two were euthanized, and 1 died within approximately 48 hr after onset of clinical signs. The salient histologic changes consisted of neutrophilic trigeminal ganglioneuritis with neuronophagia and equivocal intranuclear inclusion bodies. Pseudorabies virus was isolated from fresh tissues from 2 of the dogs, and immunohistochemistry detected the virus in the third dog. Virus sequencing and phylogeny, based upon available GenBank sequences, revealed that the virus was likely a field strain that was closely related to a cluster of PRV strains previously identified in Illinois. Though eradicated from domestic swine in the United States, PRV is present in populations of feral swine, and should therefore continue to be considered a possible cause of disease in dogs and other domestic animals with compatible clinical history and signs. Continued surveillance is necessary to prevent reintroduction of PRV into domestic swine.

Immunohistochemical Expression of c-KIT Protein in Feline Soft Tissue Fibrosarcomas

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P = .141, X 2 = 2.166), survivability (P = .241, X 2 = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P = .074, X 2 = 3.184).

Emerging Viral Encephalitides in Dogs and Cats

Few viral pathogens resulting in encephalitis in dogs and cats have emerged over the past decade or so. All are the result of penetration through presumed species barriers and all are considered zoonoses or possible zoonotic pathogens. In all cases, encephalitis is a rare event that has low morbidity but high mortality. More viruses are likely to emerge as pathogenic in our domesticated carnivorous companions as our habitats continue to overlap with the shrinking wildlife habitats. Hopefully, however, none reach the level of distinction that was once held by rabies virus.

Clinical approach to abortion, stillbirth, and neonatal death in dogs and cats

This article reviews post-mortem examination, sample collection, and diagnostic procedures used to determine the cause of abortion, stillbirth, and neonatal death in dogs and cats.

Collection and Preparation of Dog and Cat Ears for Histologic Examination

Most veterinary textbooks provide very little guidance regarding ear sampling, processing, and examination. The complexity of the ear, which includes integument, mucosa, cartilage, bone, and neural tissues, and the special procedures required to allow histologic examination are 2 of the more common reasons for reluctance by clinicians and pathologists to thoroughly assess the ear. This article helps demystify both the collection and preparation of ear samples, and briefly describes gross features and key landmarks of the ear. However, it is not the intent to provide an exhaustive account of normal and pathologic findings.

Gross Lesions of Alimentary Disease in Adult Cattle

The purpose of the gross necropsy examination of the gastrointestinal tract is to recognize the presence of lesions, thus requiring a basic understanding of its normal appearance and anatomy. This article highlights gross changes to the gastrointestinal tract of adult cattle that help place the disease processes into broad categories. Although few gross lesions reach the zenith of pathognomonic, there are numerous lesions that, when considered in aggregate with history (eg, number of animals affected, environment, duration of signs, time of onset relative to management changes, previous management) and clinical signs, can help narrow the spectrum of causes, provide a basis for a strong presumptive diagnosis, and focus diagnostic test selection.

Otology and otic diseases.

It has been 8 years since Veterinary Clinics of North America: Small Animal Practice covered the topic of ear diseases. That issue provided a comprehensive review of the normal and diseased ear, incorporating advances in technology with regard to diagnosis of disease, such as endoscopic otoscopes, as well as advanced imaging techniques, including CT and MRI. A majority of the articles focused on external ear disease but few dealt with the other portions of the ear. Our goal is to provide an issue that is complementary to the previous issue on ear disease with a primary focus on the middle and internal ear. The reader may find the word “internal” to be an unfamiliar term and may be accustomed to the “inner” ear. However, derived from Latin roots, the different compartments of the ear include auris externa or external ear, auris media or middle ear, and auris interna or internal ear. This issue begins with a brief review of anatomy and physiology of the ear to provide a foundation for the remainder of the issue. Given the paucity of publications that describe pathology of the middle and internal ear, we address this by providing anatomic landmarks and methods for collecting and processing the middle and internal portions of the ear as part of the necropsy exam. This is followed by an article about primary secretory otitis media, a relatively newly described disease that mainly afflicts Cavalier King Charles spaniel dogs and an article on otic masses. Next, there are 5 articles that specifically address conditions of the internal ear beginning with neurological manifestations of ear disease followed by feline deafness, canine deafness, canine hearing loss management, and electrodiagnostic evaluation of auditory function. The final article of this issue is an account of the causes and mechanisms of otoxicity. Where appropriate, glossaries have been included as part of the articles, which are highly specialized or use terminology that may be unfamiliar to most. Wewould like to thank Elsevier/Saunders for publishing this issue and John Vassallo for his guidance, support, and patience throughout its development and production. The editors are exceedingly grateful to all of the authors for their dedication and diligence in contributing exceptional articles for this issue. Additionally, Dr Njaa would