Abstract:
Lymphoid organs are now recognized as the major reservoir of HIV and SIV viruses in the organism. To elucidate the initial pathogenic events in these organs, we performed a quantitative follow up of viral load and pathologic changes in lymph nodes (LN) early in the course of SIV infection. 8 Rhesus macaques were inoculated intravenously with 3.10(3) TCID50 (4 animals) or 10 TCID50 (4 animals) of the SIVmac251 isolate. LN and PBMC were collected at days 7, 14, 35, and 68 p.i. and analyzed by in situ hybridization and immunohistochemistry. The initial viral load in LN was comparable for the 4 high-dose animals, with a mean number of 50 infected cells per mm2 of tissue section at 7 days p.i. However, infection in these 4 animals evolved differently. In 3 cases, high levels of viral RNA persisted in the germinal centers (GC) of the follicles at 14, 35 and 68 days p.i. The animal with the highest viral load in GC and persistence of productively infected cells in the LN parenchyma showed a rapid course of disease and had to be sacrificed at 255 days p.i. Among the other 2 animals, one showed signs of disease progression such as marked CD4 loss while the other had episodes of thrombocytopenia. For the 4th animal, which has remained healthy, viral RNA persisted in low amounts in the GC at 35 days p.i., and was no longer detectable from 68 days p.i. onwards. Immunolabelling of LN sections showed that rapid disease evolution was associated with a marked increase in the number of activated macrophages in the sinuses, detectable as early as 7 days p.i., and with the presence of CD8+ cell foci in the germinal centers. A similar study is in progress for the 4 low dose animals. Initial results show that the viral load reached in LN is as high as with a larger inoculum, though the peak of infected cells appears one week later. In conclusion, this study suggests that the determination of viral load in LN early in infection could represent a valuable indicator of the risk of progression towards the clinical stage of the infection.
Keywords: Animal Antigens, CD4/ANALYSIS Antigens, CD8/ANALYSIS Immunohistochemistry In Situ Hybridization Lymph Nodes/*MICROBIOLOGY/PATHOLOGY Macaca mulatta RNA, Viral/ANALYSIS Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY/PATHOLOGY/ *PHYSIOPATHOLOGY SIV/GENETICS/*ISOLATION & PURIF/PHYSIOLOGY T-Lymphocyte Subsets/IMMUNOLOGY Time Factors ABSTRACT 940730
M9470902
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