Abstract
Poly-Polyomaviruses
Pathologists are uniquely suited to identify lesions that are likely to be infectious, and veterinary pathologists are taking advantage using both traditional and new molecular methods of discovery. Both strategies have generously contributed to the growing family of animal polyomaviruses. Focused virus hunting by consensus polymerase chain reaction led to the discovery of raccoon polyomavirus, which is associated with brain tumors in raccoons, 1 and in this issue, Jennings et al 4 describe a nephritis associated with a novel equine polyomavirus. Both polyomaviruses have a genomic structure and gene organization similar to that of the canonical polyomavirus simian virus 40 (SV40), but significant differences in sequence might have an impact on viral life cycle and species or cell tropism. If these new veterinary species prove to be causative, whether oncogenic (raccoon) or cytolytic (horse), they are an excellent mirror for important human polyomaviruses that also are implicated in cancer (Merkel cell polyomavirus, JC virus) and nephritis (BK virus). More than 50 years of research on SV40 and murine polyomavirus provide a deep and broad foundation for the study of any newly discovered polyomaviruses. The first step is proving causation, and in the case of the ubiquitous human polyomaviruses, this has been quite tricky. Regardless, it would be worth the struggle, since natural animal infections are suitably poised to confront the big unanswered polyomavirus questions about mechanisms of persistence and viral reactivation.
Treatment and Survival in Canine Lymphoma: Specific Diagnosis Matters
In this issue of Veterinary Pathology, Valli et al 7 provide a comprehensive overview of the relationship between lymphoma subtype, survival, and treatment response in dogs. Treatment protocols were divided into prednisone alone or chemotherapeutic protocols with or without hydroxydaunorubicin. Dogs with intermediate but not high-grade lymphomas benefited from intensive chemotherapy protocols. Interestingly, survival in dogs with low-grade lymphoma was actually decreased by chemotherapy. Within these larger categories, progression and treatment response varied significantly by tumor subtype, underscoring the requirement of tumor immunophenotyping (CD3, CD79a, and CD18 immunohistochemistry) for accurate diagnosis. In addition, because this study rests on classification of lymphomas using World Health Organization (WHO) criteria, a solid knowledge of current lymphoma classification in the dog is required. Two well-illustrated publications by Ponce et al 6 and Valli et al 8 provide a recent overview of the evolution of Kiel, Revised European American Lymphoma Classification (REAL), and WHO classifications in dogs.
Maturity Matters
The physical and cellular components of respiratory innate immunity and the impact of maturation on effective immune activity are reviewed in this issue. 2 First-line respiratory defenses against the external environment are varied and include mucous secretions and the mucociliary apparatus, serum products, epithelial cells, and various immune system cells. These complex and highly regulated interactions are discussed in the context of the neonatal lung, challenged by respiratory syncytial virus (RSV), the most common cause of lower respiratory tract infection in children and a common respiratory pathogen in other domestic animals. Disease severity correlates with the inability of the immature lung to mount an effective innate immune response. 3 In the absence of an approved RSV vaccine or effective therapies, the role of an efficacious innate immunity is essential.
More than Pneumonia!
The association between pulmonary inflammation and lung cancer is well established; however, although 90% of lung cancer is attributed to tobacco smoking, only 10% to 15% of smokers develop lung cancer, which suggests other risk factors independent of smoking. One of these factors is chronic pulmonary inflammation (many smokers have chronic obstructive pulmonary disease). Unfortunately, few models examine the effects of inflammation-related lung cancer in humans. In their article, Melkamu and colleagues 5 examine the chronic intranasal instillation of lipopolysaccharide (LPS) to mice treated with a carcinogen. LPS is ubiquitous in the environment, including soil, plants, water, dust, and ambient air. The research model described an increase in the multiplicity of larger tumors and histopathologically more advanced lesions (adenoma with dysplasia and adenocarcinoma) as well as increased lung infiltration by macrophages in treated animals. In addition, an increase was noted in inflammation marker expression, cell proliferation, and survival-related proteins. LPS dramatically increased the recruitment of F4/90+ macrophages into the carcinogen-induced lung tumors. This research illustrates the detrimental effects of inflammation, causing genetic and epigenetic alterations contributing to neoplasia.