The Human Immunodeficiency Virus tat Gene Enhances Replication of Human Herpesvirus-6

Human herpesvirus-6 (HHV-6) can enhance the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) in cells doubly infected by HIV-1 and HHV-6. HHV-6 enhances transcription of the HIV-1 long terminal repeat, and several HHV-6 trans-activator genes have been identified. Since HIV-1 and HHV-6 have similar cellular tropism, and since HIV-1 trans-activates other herpesviruses, a reciprocal interaction between the two viruses is possible. Interactions between HIV-1 and HHV-6 were analyzed in human umbilical cord blood (CB) lymphocytes and in a T-cell line by transfaction and infection experiments. CB cells dually infected with HIV-1 and HHV-6 showed an increase in HHV-6 infectious titer, an increase in HHV-6-specific immediate early RNA, and an increase in HHV-6 protein synthesis. Similarly, T-lymphocyte cells transfected with the entire HIV-1 proviral genome displayed an increase in HHV-6. When T-cells were transfected with a plasmid containing the HIV-1 tat gene under control of the simian virus (SV40) promoter and infected with HHV-6, higher levels of HHV-6 proteins and infectious virus were detected. Therefore, the presence of HIV-1 gene products, such as tat, can lead to an activation of HHV-6 expression. Since HHV-6 is cytopathic, its activation by HIV-1 may accelerate the depletion of CD4⁺ T-cells in infected individuals.