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166 Lack of Immunopathologic Responses as a Possible Protective Mechanism against Disease Development in the Natural Primate Hosts of SIV
S. Norley*1, S. Holzammer2, B. Beer3, E. Holznagel2, C. Brown3, and R. Kurth1
1Robert Koch-Inst., Berlin, Germany; 2Paul-Ehrlich-Inst., Langen, Germany; and 3 NIAID, NIH, Rockville, MD, USA
Background: Studies in the apathogenic SIVagm/ African green monkey (AGM) natural host system have shown that the antiviral immune response, cellular host range, cell-associated virus loads, and in vivo variability are similar to those seen in pathogenic systems. It was therefore necessary to establish whether AGMs indeed suppress virus replication in vivo and, if not, whether a lack of potentially harmful immunopathologic mechanisms could account for their protection from disease progression. In this regard, the apparent tolerance of many natural host species to the Gag protein of their corresponding SIV could possibly preclude the formation of immune complexes and therefore lymph node trapping and dysfunction.
Methods: A real-time quantitative PCR was developed to measure plasma virus loads in experimentally and naturally infected AGMs. Viral Gag was purified from SIVagm using affinity column chromatography. Animals were repeatedly immunized and challenged with SIVagm.
Results: The measurement of plasma viral loads in experimentally and naturally infected AGMs revealed that the levels of viremia are as high as, if not higher than, those found in HIV-1-infected humans or SIVmac-infected macaques progressing to disease. Animals immunized with purified Gag protein developed high levels of Gag-specific antibodies, which were surprisingly not maintained following productive infection. Although after 1 year there is evidence of viral trapping as visualized by in situ hybridization there has been as yet no sign of disease progression.
Conclusions: The high plasma virus loads in naturally and experimentally infected AGMs indicates that these natural hosts of SIVagm possess neither innate nor adaptive immune responses able to suppress replication to harmless levels. The unusual failure or infection to boost and maintain anti-Gag responses may indicate that endogenously processed Gag antigen is not recognized by the AGM immune system and also prevented the maintenance of high levels of viremia and Gag-specific antibodies theoretically necessary to saturate lymphoid tissues with immune complexes.
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