Simian/Human Immunodeficiency Virus sub(89.6) Expressing the Chemokine Genes MIP-1 alpha , RANTES, or Lymphotactin

We constructed replication competent, attenuated, nef-deleted SHIV sub(89.6) that express the rhesus macaque chemokine genes MIP-1 alpha , RANTES, or LTN from the nef region. The chemokine inserts were stable during several passages in CEMx174 cells and the viruses grew well in activated rhesus PBMC. Expression of virally encoded MIP-1 alpha , RANTES, or LTN was detected in culture fluids from infected HOS CD4 alpha CXCR4 super(+) cells, that were used because they have a low background production of these chemokines. The in vitro growth kinetics of all nef-deleted SHIV sub(89.6) were slower than the parental strain in both CEMx174 cells and rhesus PBMC. Rhesus macaques were susceptible to SHIV sub(89.6-MIP-1 alpha ), SHIV sub(89.6-RANTES), SHIV sub(89.6-LTN), and nef-deleted control SHIV sub(89.6-dLTN) infection via the intrarectal route using standard virus doses, and intact viruses were reisolated from infected animals throughout the interval of acute infection. SHIV expressing the chemokine genes MIP-1 alpha , RANTES, or LTN may help determine the in vivo roles for these chemokines in modulating virus replication and disease.