Transactivation of human immunodeficiency virus long terminal repeat during the early phases of human cytomegalovirus infection

Abstract

Summary We have shown that human cytomegalovirus (CMV) infection increases, through transactivation, the functioning of long terminal repeat (LTR) elements of the human immunodeficiency virus (HIV) genome in vitro, a finding implying that CMV infection may be a direct co-factor in the pathogenesis of acquired immunodeficiency syndrome. Human MRC-5 fibroblasts were transiently transfected with a vector containing the LTR of the LAV-1 isolate of HIV and the gene coding for the enzyme chloramphenicol-acetyl-transferase (CAT). The HIV LTR-driven synthesis of CAT observed in control MRC-5 cells was much enhanced when the cells were infected with the AD169 strain of human CMV. In contrast, CAT synthesis driven by regulatory sequences from either mouse mammary tumour virus or hepatitis B was not increased. The effects of CMV were clearly associated with the early phases of infection (before CMV DNA replication occurs), since it was observed as early as 8 h after infection in CMV-permissive MRC-5 cells, and in non-permissive LTK cells which expressed only immediate-early and early CMV antigens. Our results indicate that, even under non-permissive conditions, CMV is able to transactivate HIV LTR, a finding which opens up the possibility that co-infection of human cells in vitro with both viruses results in enhanced replication of HIV, even in cell types with low permissivity to CMV.