Infectious Agent Update: Charles River Pinpoints Pneumocystis carinii as the Causative Agent for "RRV"
September 2, 2010 - Charles River continually performs research studies on many aspects of laboratory animal science. One such study has led to the conclusion that Pneumocystis carinii (Pc) is the causative agent for interstitial pneumonia in laboratory rats, previously known by the working name "rat respiratory virus" or "RRV". This work has been submitted for publication and will be presented at the 61st AALAS National Meeting. The presentation, "Determination of Optimal Sample Types and Time Points for the Detection of Pneumocystis carinii in Rats by Real-Time PCR", is part of the Laboratory Investigations 2 platform session, and is scheduled for Wednesday, October 13th at 3:15 PM (Program Number PS75).
History of Pc/"RRV" interstitial pneumonia in laboratory rats
First appearing in literature in the mid-1990s, reports described an apparently novel and prevalent pulmonary disease which compromised inhalation toxicology studies in immunocompetent laboratory rats. This entity was characterized by lymphohistiocytic interstitial pneumonia and perivascular lymphocytic cuffing throughout the lung. More recently, researchers at Charles River published histopathologic criteria for diagnosis and described the consistent progression of lesions over time [Albers et al., Vet. Pathol. 46 (5), 992-9 (2009)]. This and other observations have led many to conclude that the causative agent is transmissible.
Charles River research study overview
In order to investigate the etiological agent, Charles River researchers first established two consistent sources of infected rats within isolators. At predetermined times after exposure, specimens were collected from exposed rats and analyzed using molecular-based techniques to screen for novel viral sequences. As no viral sequences were detected, attention turned to non-viral etiologies.
When examining the lungs of athymic nude rats exposed to rats in the "RRV"-positive isolators, high levels of Pc were noted. Although Pc had not been found by PCR in affected tissues by other researchers, it was considered as a candidate in this study because it is a pulmonary agent present in the study isolators and absent from Charles River rat colonies, all of which are negative for "RRV".
A quantitative PCR study of Pc in "RRV" lesion-positive rat lungs demonstrated a strong association between Pc and the interstitial pneumonia; findings were confirmed by the detection of Pc in archived "RRV"-positive paraffin-embedded lung tissue. This study also found that the antibody response to Pc coincided with the appearance of the characteristic interstitial pneumonia and the decline of Pc populations. Based on the evidence, we propose that the causative agent of the histologic lesions lumped into the disease entity "RRV" is Pneumocystis carinii.
Health status and testing of Charles River rat colonies
All Charles River rat colonies worldwide are negative for Pc. These colonies have been negative for interstitial pneumonia lesions for more than two years, and are currently screened quarterly by histopathology for the presence of lung lesions. Elucidation of Pc as the causative agent of "RRV" does not change the colony status of Charles River animals or the frequency of screening, but only the name of the disease and the method by which the animals are screened. Histopathologic screening for "RRV" will be phased out in lieu of a combination of PCR and serology for Pc.
Diagnostic testing available for screening laboratory rat colonies
Charles River offers multiple diagnostic tools to screen for Pc:
- NEW: Serology via Indirect Fluorescent Antibody (IFA) test*
- TaqMan® PCR, both as an individual agent test and as part of the Charles River Prevalent Rodent Infectious Agent (PRIA) PCR Panel
- Histology of lung tissue (if necessary)
*Note: Tests on additional serology platforms are in development.
Contact us
Your research has never been more important, which is why Charles River is committed to providing the critical resources that you need. If you have any questions or require further information, please contact us at askcharlesriver@crl.com or by phone at 1.877.274.8371 (US and Canada) or +800.3195.3430 (International) - our professional staff members are available to discuss your specific needs.
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