Simian/human immunodeficiency virus89.6 expressing the chemokine genes MIP-1α, RANTES, or lymphotactin

We constructed replication competent, attenuated, nef-deleted SHIV89.6 that express the rhesus macaque chemokine genes MIP-1alpha, 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-1alpha, RANTES, or LTN was detected in culture fluids from infected HOS CD4(+) CXCR4(+) cells, that were used because they have a low background production of these chemokines. The in vitro growth kinetics of all nef-deleted SHIV89.6 were slower than the parental strain in both CEMx174 cells and rhesus PBMC. Rhesus macaques were susceptible to SHIV89.6-MIP-1alpha, SHIV89.6-RANTES SHIV89.6-LTN, and nef-deleted control SHIV89.6-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-1alpha, RANTES, or LTN may help determine the in vivo roles for these chemokines in modulating virus replication and disease.