Session 18Oral Abstract Presentations Viral Neuropathogenesis Session Day and Time: Wednesday 10 am - 12:30 pm Presentation Time: 10:45 Room: Ballroom C
89 Systemic Macrophage Infection Associated with Development of SIV Encephalitis S. J. Bissel*, G. Wang, A. M. Trichel, M. Murphey-Corb, C. A. Wiley Univ of Pittsburgh, PA
Background: A fraction of SIV-infected macaques develop SIV encephalitis during the late stages of immunosuppression. Pathologically, SIV encephalitis is characterized by the presence of activated and SIV-infected macrophages. It is believed that SIV encephalitis might develop as the result of increased trafficking of activated and SIV-infected monocytes into the brain. Currently, the relationship between monocyte/macrophage infection outside of the brain and the development of SIV encephalitis is unknown. We hypothesized that macaques that develop SIV encephalitis have more infected monocyte/macrophages in blood and lymph nodes throughout the evolution of SIV infection.
Methods: In an attempt to hasten disease progression and increase the incidence of encephalitis, we have taken advantage of an in vivo CD8 depletion paradigm. We have CD8 depleted 2 pigtailed macaques during chronic SIV infection and 8 rhesus macaques at the time of infection. Blood monocytes, lymph nodes, and CSF were longitudinally collected in order to assess viral infection using p27 ELISA, immunohistochemistry, and real-time RT-PCR. Statistical analyses were performed by 2-way, unpaired Student’s t-test.
Results: Four (4) of 7 all CD8+ T-cells were depleted from the blood for 2-4 wks. Throughout the time course of infection, lymph nodes from the encephalitic pigtailed macaque had greater numbers of infected macrophages than the pigtailed macaque that did not develop encephalitis. In the rhesus macaque model, lymph nodes from the encephalitic macaques had greater numbers of infected macrophages at earlier time points of infection than macaques that did not develop encephalitis. In vitro, blood monocytes isolated from encephalitic macaques produced significantly more SIV p27 upon differentiation into macrophages than monocytes from macaques without encephalitis.
Conclusions: These results support our hypothesis that macaques that develop encephalitis have more infected monocyte/macrophages outside of the brain during the evolution of SIV infection.
