Activation of HIV transcription by human foamy virus in transgenic mice.

BACKGROUND

Although infection by HIV-1 is the primary cause of AIDS, cofactorial agents of an infectious nature may be involved in the pathogenesis of the disease. The present work addresses the cofactorial potential of human foamy virus (HFV) in AIDS. It has been suggested that HFV seroprevalence reaches 5% in East Africa, and HFV seroprevalence in East African patients suffering from AIDS and AIDS-related complex may be as high as 20%. Although the pathogenic potential of HFV in humans has not yet been investigated in detail, HFV transgenic mice develop an encephalopathy reminiscent of some of the features of HIV-associated brain diseases.

EXPERIMENTAL

DESIGN

We set out to investigate the possibility that the regulatory genes of HFV may act as transcriptional cofactors of HIV. To study the effects of bel1, the transcriptional activator of HFV, on the HIV-1 LTR, we generated double transgenic mice for bel1 and for the HIV-1 LTR linked to a lacZ reporter gene. Moreover, to identify the cis-acting elements mediating bel1 action on the HIV LTR, we analyzed the consequences of deletions in the negative regulatory element or in the NF-kappa B binding sites.

RESULTS

We demonstrate that bel1 is capable of activating the transcription of HIV-1 LTR in vivo. Such transactivational activity, however, was observed exclusively in a subset of hippocampal neurons, whereas cortical neurons expressing bel1 did not show transactivation. Transactivation was completely abolished by the deletion of the NF-kappa B binding sites. In contrast, deletion of the negative regulatory element region seems to enhance transactivation of bel1 on HIV-1 LTR over a prolonged period of time.

CONCLUSIONS

Our study indicates that transcriptional transactivation of HIV-1 by HFV can be accomplished in vivo and is dependent on NF-kappa B binding sequences. Therefore, transcriptional transactivation is a potential mechanism of cooperation between HFV and HIV. It is conceivable that this phenomenon attains clinical significance in a situation of coinfection with both viruses.