Abstract
Measles virus is a highly contagious member of the Morbillivirus genus in the Paramyxoviridae family. The virus is thought to infect the apical side of epithelial cells of the upper respiratory tract before spreading in lymphoid cells. The authors of this report investigated an alternative hypothesis that primarily infected lymphoid cells carry the virus to the basolateral surface of the respiratory epithelial cell. They determined the residues of the measles virus attachment protein to the epithelial cell receptor (EpR) and created an EpR-blind virus that still maintained its ability to enter lymphoid cells expressing the signaling lymphocytic activation molecule (SLAM; CD150). Rhesus monkeys inoculated intranasally with the mutant virus developed rash, anorexia, and viremia; however, they did not shed virus in the airways. In vitro studies using well-differentiated human airway epithelial cells with tight junctions demonstrated that wild-type measles virus was infective only when applied basolaterally, while the EpR-blind cells lacked infectivity. The authors conclude that EpR is likely a basolateral protein of respiratory epithelium, and that infection of the respiratory epithelium is not essential for systemic spread and virulence of measles virus.
Leonard VHJ, Sinn PL, Hodge G, et al., Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. J Clin Invest
Horses with the Gray phenotype are born with hair pigmentation but lose this pigmentation prematurely, and by the age of 6–8 years they have white hair while retaining pigmentation in their skin. For generations, humans have selected for the Gray mutation in order to eventually obtain horses with the white coat color. However, these horses are also predisposed to develop dermal melanomas. Pielberg and colleagues hypothesized that these conditions are related and are due to a single mutation that occurred a long time ago. They discovered a 4.6 kilobase duplication in intron 6 of the STX17 (syntaxin-17) gene that they speculate is a cis-acting mutation causing overexpression of both STX17 and a neighboring gene, NR4A3 (nuclear receptor subfamily 4, group A, member 3), in melanomas from Gray horses. The duplication was present in more than 800 Gray horses tested, but in none of the non-Gray horses. Although the mechanism(s) whereby this mutation leads to depigmentation and melanoma formation is only speculated upon, there is substantial evidence that NR4A3 is involved in the cell cycle, and STX17 may interact with RAS. This work demonstrates how selective breeding can lead to unintended phenotypes.
Pielberg GR, Golovko A, Sundstrom E, et al. . A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat Genet
African lions have been struck by two recent outbreaks of canine distemper virus (CDV) that caused an unusually high mortality rate—one outbreak occurred in 1994 and the other in 2001. The authors investigated possible reasons that could explain the high mortality, as serologic evidence suggested that other outbreaks of CDV in lions were not associated with clinical signs or lethality. They discovered that concurrent hemoparasitism with Babesia correlated with both of the high mortality epidemics. Both epidemics were preceded by extreme drought and massive die-offs of herbivores, particularly the Cape buffalo. When the rains resumed, the tick population on the starving buffalo expanded and lions were infected by high numbers of Babesia, which coincided with the CDV outbreaks. This elegant epidemiologic investigation demonstrates the complex balance between climate conditions and host–pathogen relationships, and how climate extremes can dramatically lead to multi-pathogen epidemics with unprecedented mortality.
Munson L, Terio KA, Kock R, et al. . Climate extremes promote fatal co-infections during canine distemper epidemics in African lions. PLoS ONE
Counting ovarian follicles is one method to assess ovarian toxicity in rat reproductive toxicity studies. Manual counting on slides stained with hematoxylin and eosin (H&E) is the industry standard, but primordial and primary follicles can be difficult to see by this method and there can be significant interobserver variability. Enhancement of the follicles by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and Cytochrome P450 1B1 (CYP1B1) is sometimes performed, but assessment is still done by manual counting. Here the authors compared results of semi-automated image analysis on rat ovarian tissue sections stained with H&E and PCNA to manual counting of the same slides. Results obtained with the semi-automated image analysis and Image Pro software on PCNA-stained sections were similar to manual counting, with the advantages of high reproducibility and decreased variability. This technique may be applicable to ovaries of other species.
Picut CA, Swanson CL, Scully KL, et al. . Ovarian follicle counts using proliferating cell nuclear antigen (PCNA) and semi-automated image analysis in rats. Toxicol Pathol
Histopathologic evaluation of endoscopic biopsies is frequently performed as part of the diagnostic workup of gastrointestinal diseases in companion animals. In this study the authors hypothesized that quality of the endoscopic biopsy samples affects the ability to demonstrate a lesion in the stomach or duodenum, and that a greater number of endoscopic samples is required if the tissue specimens are of poor quality. Tissues from 99 dogs and 51 cats from a total of 8 institutions in 5 countries were examined for quality of the section (rated as inadequate, marginal, or adequate), type of lesion (lymphangiectasia, crypt lesions, villus blunting, or cellular infiltrate), and severity of lesion (normal, mild, moderate, or severe). In general, fewer samples were required as the quality of the sections improved. However, determination of moderate duodenal infiltrates in feline samples was not dependent on sample quality. Nor were moderately severe gastric lesions in cats. The authors conclude that the quality of endoscopic biopsies has a marked effect on their sensitivity for identification of certain lesions, and that there are differences between biopsies from cats and dogs.
Willard MD, Mansell J, Fosgate M, et al. . Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats. J Vet Intern Med