SIV Persistence but Lack of Disease in the Natural Primate Hosts of SIV

Reinhard Kurth and Stephen Norley; Robert Koch-Institute, Nordufer 20, Berlin (Germany)

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, it seemed possible that the apparent tolerance of many natural host species to the Gag protein of their corresponding SIV could preclude the formation of immune complexes and therefore lymph node trapping and dysfunction. Material and 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 that were surprisingly not maintained following productive infection. Although after one year there was 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 of infection to boost and maintain anti-Gag responses may indicate that endogenously processed Gag antigen is not recognized by the AGM immune system. Investigations into the cellular immune responses to SIVagm proteins (particularly Gag) are being performed to elucidate the precise nature of this dysfunction and it's possible protective role.