Molecular Localization Techniques in the Diagnosis and Characterization of Nonhuman Primate Infectious Diseases

Abstract

Molecular localization techniques remain important diagnostic and research tools for the pathologist evaluating nonhuman primate tissues. In situ hybridization and immunohistochemistry protocols have been developed for many important pathogens of nonhuman primates, including RNA and DNA viruses, prions, and bacterial, protozoal, and fungal pathogens. Such techniques will remain critical in defining the impact and relevance of novel agents on animal health and disease. A comparative pathology perspective often provides valuable insight to the best strategy for reagent development and can also facilitate interpretation of molecular localization patterns. Such a perspective is grounded in a firm understanding of microbe-host pathobiology. This review summarizes current molecular localization protocols used in the diagnosis of selected primate infectious diseases.

Impact of the Genetics and Source of Preclinical Safety Animal Models on Study Design, Results, and Interpretation

“…Lastly, but by no means least, environmental factors including early or later exposure to pathogenic or nonpathogenic infectious agents, microbiome, dietary, and other local ecosystem variability (such as ambient temperatures, water source, indoor/outdoor access), and effects of social hierarchies in group-housed animals can all contribute to the ultimate response of an animal to any given stimulus or a xenobiotic. Animals from the same original breeding colony but housed in varying holding colonies, or sourced from different vendors and mixed in one holding facility can have variable background incidences of, and exposures to, bacterial, viral, parasitic, and fungal agents, resulting in different susceptibility to pathogens and/or innate immune responses once placed together on study (Mansfield, Sasseville, and Westmoreland 2014;Sasseville and Mansfield 2010;Sasseville and Diters 2008;Sasseville et al 2012;Saravanan, Sasseville, and Mansfield 2015).…”

Nonhuman Primates

“…Histologically, neutrophilic infiltrates are observed with large cytomegalic cells containing intranuclear and intracytoplasmic viral inclusions (Hutto et al, 2004) (Fig. While these findings are diagnostic, immunohistochemistry may be used to confirm infection (Mansfield et al, 2014). While these findings are diagnostic, immunohistochemistry may be used to confirm infection (Mansfield et al, 2014).…”

“…Immunohistochemistry for viral proteins EBNA2 and BZLF1 can be done on biopsy specimens to confirm infection and establish an etiologic diagnosis (Mansfield et al, 2014). Immunohistochemistry for viral proteins EBNA2 and BZLF1 can be done on biopsy specimens to confirm infection and establish an etiologic diagnosis (Mansfield et al, 2014).…”

“…If doubt exists as to the identity of the basophilic organism, IHC can be used for confirmation (Mansfield et al, 2014). There are often neutrophilic infiltrates surrounding and infiltrating bile ducts.…”

Biologic Immunomodulatory Drugs and Infection in the Respiratory Tract of Nonhuman Primates

“…Special investigations are the only way to diagnose the pathogen involved. 82 For this purpose, specific sampling is normally needed. But if not performed, the left over blood samples or formalin-fixed, paraffin-embedded tissue might be used.…”