ExperimentalPneumocystis cariniiPneumonia in Simian Immunodeficiency Virus–Infected Rhesus Macaques

Abstract

To establish experimental Pneumocystis carinii infection in simian immunodeficiency virus (SIV)-infected macaques as a model of acquired immunodeficiency syndrome (AIDS)-associated P. carinii pneumonia (PCP), SIV-infected macaques were inoculated intrabronchially with macaque-derived P. carinii, and P. carinii-specific polymerase chain reaction (PCR) and flow cytometric analysis of bronchoalveolar lavage fluid were done biweekly for up to 44 weeks after inoculation. All inoculated animals had a P. carinii-specific PCR product after infection. CD8(+) T cells in lung lavage samples from SIV- and P. carinii-coinfected animals increased to >90% of total CD3(+) cells, a pattern associated with naturally acquired P. carinii infection. Progression of disease also was correlated with increased neutrophil infiltration to the lungs. The animals had a protracted period of asymptomatic colonization with P. carinii before progression to PCP. The development of a model of PCP in SIV-infected rhesus macaques provides the means to study AIDS-associated PCP.

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…In laboratory rodents, nested PCR of oral swabs has demonstrated that close to 100% of adult rats are colonized with Pneumocystis shortly after receipt (127). Similarly, spontaneous colonization occurs in both free-living and laboratory nonhuman primates (23,44,63). In a free-living macaque colony, all animals had detectable colonization at some point over a 2-year observation period, and the duration of colonization averaged 2 months (63).…”

Genetic Variation at the Mitochondrial Large-Subunit rRNA Locus of Pneumocystis Isolates from Simian Immunodeficiency Virus-Infected Rhesus Macaques

“…Recently, our laboratory has developed an experimental model of Pneumocystis infection in rhesus macaques (4). In these studies, Pneumocystis was introduced intrabronchially, and the progression of infection was monitored by Pneumocystis-specific PCR of BAL fluid (4).…”

“…Recently, our laboratory has developed an experimental model of Pneumocystis infection in rhesus macaques (4). In these studies, Pneumocystis was introduced intrabronchially, and the progression of infection was monitored by Pneumocystis-specific PCR of BAL fluid (4). In addition to its usefulness as a diagnostic probe, the sequence variability at the mt LSU locus allows for the distinction between the presence of the inoculating strain and a naturally acquired infection in this model.…”

“…This extended colonization period and the indolent course of the infection are very similar to those of HIV-associated PCP. Naturally acquired and experimental PCP in SIV-infected macaques shows histopathologic features similar to those seen in HIV-associated PCP (1,2,4,7,13).…”

“…To study the interaction of Pneumocystis and HIV in the pathogenesis of lung injury and to define immune parameters associated with the control of PCP in the context of HIV infection, our laboratory has developed a nonhuman-primate model of PCP in SIV-infected rhesus macaques (4). In these studies, conditions for reproducible infection were established and the progression of Pneumocystis infection was characterized.…”