The effects of HIV-1 Tat protein on mycobacterial infection

Abstract

Human immunodeficiency virus infection remains a worldwide threat. With the emergence of HIV-1 induced immunodeficiency in the host, mycobacterial infection becomes a common opportunistic infection as its prevalence is dramatic increased. HIV-1 Tat is an important viral regulatory protein in promoting HIV replication and modulating the cytokine production, as demonstrated by our previous publications. In light of that, we would like to investigate whether HIV-1 Tat could affect mycobacteria induced immune responses. We first examined whether HIV-1 Tat could mediate mycobacteria induced cytokine production. The results demonstrated that HIV-1 Tat suppressed mycobacteria-induced TNF-α in human primary macrophage. Next, we examined whether HIV-1 Tat also suppress the intracellular survival of mycobacteria. Under the pretreatment of HIV-1 Tat in human primary macrophages, intracellular growth of mycobacteria was enhanced significantly. Since TNF-α is proposed to regulate mycobacterial survival, we would like to verify this hypothesis in order to provide the evidence to support our findings that HIV-1 Tat downregulated mycobacteria induced TNF-α is participated in suppressing the mycobacterial survival. The results showed that when we neutralized the mycobacteria produced TNF-α by antibodies, the survival of mycobacteria is increased. In summary, HIV-1 Tat may play a role in favouring mycobacterial opportunistic infection during AIDS progression.