SIVagm containing the SHIV89.6P Envelope gene replicates poorly and is non-pathogenic

Area of Science:

• Virology
• Immunology
• Primate Lentiviruses

Background:

• Simian immunodeficiency virus (SIVagm) is non-pathogenic in African green monkeys (AGMs).
• Hybrid simian-human immunodeficiency virus SHIV89.6P, containing the HIV env gene, causes rapid disease in rhesus macaques.
• The role of the HIV env gene in enhancing pathogenicity within a non-pathogenic lentiviral context is not fully understood.

Purpose of the Study:

• To investigate if the HIV env gene enhances disease pathogenicity when incorporated into the non-pathogenic SIVagm lentivirus.
• To construct and characterize a chimeric lentivirus (SHIV-MP) containing the SIVagm backbone and the HIV 89.6P env gene.

Main Methods:

• Construction of a full-length chimeric lentivirus genome (SHIV-MP) combining SIVagm and HIV 89.6P env.
• In vitro replication studies in simian peripheral blood mononuclear cells (PBMCs).
• In vivo inoculation of AGMs, rhesus macaques, and pig-tailed (PT) macaques to assess viral replication and CD4(+) T lymphocyte counts.

Main Results:

• SHIV-MP exhibited replication kinetics similar to SIVagm in simian PBMCs.
• Inoculated monkeys (AGMs, rhesus, PT macaques) maintained normal CD4(+) T lymphocyte counts.
• Peak levels of productively infected cells in SHIV-MP-infected monkeys were significantly lower (10-100 fold) than in SIVagm-infected macaques.

Conclusions:

• The HIV env gene from SHIV89.6P appears insufficient to confer acute pathogenicity to the non-pathogenic SIVagm lentivirus.
• Poor in vivo replication of the chimeric virus likely contributes to its lack of pathogenicity.