Acute SIV Infection in Sooty Mangabey Monkeys Is Characterized by Rapid Virus Clearance from Lymph Nodes and Absence of Productive Infection in Germinal Centers

Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency

Localization of SIV infected cells in LN from SM and PM.

<p>Infected cells, as quantified by ISH for SIV RNA. Histomorphological localization of infected cells (identified by dark blue NBT/BCIP chromogen) in GC versus paracortical microenvironments was accomplished by microscopic analysis of Nuclear Fast Red counterstain. Scoring is based on the average for each group at each time point, divided into quartiles (+; 0–5/mm²) (++; 6–15/mm²); (+++; 16–50/mm²); (++++; >50/mm²) derived from quantitative measurements. Asterisk (*) Indicates one germinal center contained an SIV-infected cell at 2, 6, and 24 wpi in a CD8 depleted SM. Numbers of GC evaluated at each time-point is indicated by n values.</p