LIMITED VIRAL SPREAD AND RAPID IMMUNE-RESPONSE IN LYMPH-NODES OF MACAQUES INOCULATED WITH ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS

A comparative study was undertaken to characterize the very early even ts that distinguish attenuated and pathogenic simian immunodeficiency virus (SIV) infections. Three rhesus macaques were inoculated with the attenuated SIVmac 251 Delta nef virus, and three others with a virus of intermediate phenotype, SIVmac 239 nef stop. They were compared to four macaques inoculated with the pathogenic SIVmac 251 isolate. Lymph nodes (LN) taken between 7 days and 2 months postinoculation were ana lyzed for SIV expression by in situ hybridization. During acute infect ion, SIV 251 Delta nef infected 1 to 1.5 log(10) fewer cells in SIV ti ssue than the pathogenic SIV 251 isolate. The reduction was more marke d in the blood, as SIV 251 Delta nef infected 2 to 3 logic fewer PBMC than the isolate and did not yield detectable antigenemia. Morphometri c measurements showed that the development of germinal centers (GC) wa s more rapid in the Delta nef infection, which led to a more efficient trapping of viral particles, and could account for antigenemia cleara nce. The SIV 239 nef stop clone reverted to a nef(+) genotype at Week 2, but induced a lower viral burden than a directly pathogenic virus. The kinetics of GC development was rapid, indicating that SIV 239 nef stop induced an immune response similar to that seen in attenuated inf ection. This study provides evidence that attenuated SIV elicits a mor e rapid immune response than pathogenic SIV and suggests that an early immunosuppressive episode may facilitate the dissemination of pathoge nic SIV. (C) 1995 Academic Press, Inc.