Simian/Human Immunodeficiency Virus 89.6 Expressing the Chemokine Genes MIP-1 α,RANTES,or Lymphotactin

Abstract

We constructed replication competent, attenuated, nef-deleted SHIV_89.6 that express the rhesus macaque chemokine genes MIP-1α, 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-1α, 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 allnef-deleted SHIV_89.6 were slower than the parental strain in both CEMx174 cells and rhesus PBMC. Rhesus macaques were susceptible to SHIV_89.6-MIP-1α , SHIV_89.6-RANTES, SHIV_89.6-LTN, and nef-deleted control SHIV_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-1α, RANTES, or LTN may help determine the in vivo roles for these chemokines in modulating virus replication and disease.