Transcriptional activation of human immunodeficiency virus type 1 by herpesvirus infection: an in vivo footprinting study.

The process of transcriptional activation directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) was investigated by in vivo footprinting using ligation-mediated polymerase chain reaction in a human epithelial cell line infected with human herpes simplex virus type 1 (HSV-1) or human herpes virus 6 (HHV-6). Infection with both viruses induces a remarkable enhancement in LTR-mediated gene expression that correlates with a change in the pattern of protein binding to the downstream kappa B site of the enhancer region. In HHV-6 infected cells, this change in the genomic footprinting pattern is concomitant with the induction of specific enhancer-binding proteins in the nucleus. The similarity of these events to those detected in other previously investigated experimental systems suggests that the LTR enhancer region is the ultimate target for the induction of the HIV-1 transcriptional response upon stimuli acting through different upstream pathways.

Human herpesviruses 6 and 7 in salivary glands and shedding in saliva of healthy and human immunodeficiency virus positive individuals.

The presence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) was investigated by the polymerase chain reaction in saliva specimens from healthy persons, donors affected by common cold or recurrent aphthous ulceration (RAU), and human immunodeficiency virus (HIV) positive patients, and in salivary gland biopsies. The sensitivity of the technique made it possible to detect as few as 5-10 target molecules in 15 microliters of saliva. HHV-6 was present in 63% of salivary gland biopsies and in 3% of salivas from healthy persons. No significant difference in the presence of HHV-6 was detected in specimens from donors with common cold, RAU, or HIV-infected patients. HHV-7 was present in 75% of salivary glands and in 55% of salivas from healthy persons. HHV-7 was detected with similar frequency in salivas from donors with common cold or RAU. Salivas from HIV-infected patients harbored HHV-7 with higher frequency (81%) and increased viral load. These results show that salivary glands are a site of persistent infection for both HHV-6 and HHV-7. However, the two viruses seem to differ in their biological properties: 1) HHV-6 is rarely present in saliva in detectable amounts, while HHV-7 is frequently detected; and 2) immunosuppression by acquired immunodeficiency syndrome (AIDS) increases the frequency of detection and the viral load of HHV-7, but does not have a significant effect on HHV-6 shedding in saliva.

Reciprocal in vitro interactions between human herpesvirus-6 and HIV-1 Tat.

The transactivation induced by human herpesvirus 6 (HHV-6) on the HIV-1 promoter was studied both in the presence and in the absence of the retroviral transactivator protein (Tat) constitutively expressed in Jurkat cells. Jurkat-tat cells were infected with HHV-6, transfected with a plasmid containing HIV-1 long terminal repeat (LTR)/chloramphenicol acetyltransferase (CAT), and CAT assays were performed. HHV-6 infection in the presence of Tat resulted in significantly higher LTR activation than that observed by Tat or HHV-6 alone, indicating that HHV-6 and Tat interact synergically. Furthermore, it was demonstrated that expression of HIV-1 tat inhibits HHV-6 replication, as shown by a 3.6-15.4-fold reduction in infectious yield. We suggest that HHV-6 could trigger HIV reactivation in HIV-seropositive patients which, in turn, could inhibit HHV-6 production.