Human herpes virus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer.

Abstract

Human Herpes virus‐6 (HHV‐6) can co‐infect with HIV‐1 human CD4+ T‐cells, leading to accelerated cell death, and factors in HHV‐6‐infected cells stimulate HIV‐1 LTR directed gene expression. In this study, we have examined the mechanism of HIV‐1 activation by HHV‐6 and localized the cis‐acting sequences of HIV‐1 LTR responsive to trans‐activation. Increased HIV‐1 LTR directed gene expression is obtained in HIV‐1 infected cells co‐infected with HHV‐6, or in HHV‐6 infected cells co‐transfected with the HIV‐1 tat gene. Parallel increases of HIV‐1‐specific transcripts are seen by in situ hybridization in HHV‐6/HIV‐1 doubly infected cells as compared to single HIV‐1 infection. Similarly, infection by HHV‐6 increases the steady‐state level of HIV‐1 LTR mRNA that parallels CAT enzymatic activity, suggesting a transcriptional and/or post‐transcriptional activation. Sequences necessary for HIV‐1 LTR activation by HHV‐6 are distinct from those required for that tat response and map to a region of the HIV‐1 LTR from ‐103 to ‐48. The HIV‐1 enhancer sequence (‐105 to ‐80) is sufficient to confer HHV‐6 inducibility to a heterologous promoter, and nuclear protein(s) activated or induced by HHV‐6 infection specifically bind to the NF kappa B motifs of the HIV‐1 enhancer region.(ABSTRACT TRUNCATED AT 250 WORDS)

The Genome of Human Herpesvirus 6: Maps of Unit-length and Concatemeric Genomes for Nine Restriction Endonucleases

“…Prior infection with HHV-6 has, however, been postulated as a cofactor in the progression of asymptomatic HIV-infected individuals to AIDS. Both HHV-6 and HIV infect predominantly CD4-positive T lymphocytes (Lusso et al, 1988;) and HHV-6 can both trans-activate the HIV promoter/enhancer linked to reporter genes (Horvat et al, 1989;Ensoli et al, 1989) and accelerate CD4-positive cell death in cultures co-infected with both viruses . The significance of these molecular and biological properties of HHV-6 to human disease has not yet been established.…”

Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS upon coinfection with HHV-6A

“…Several lines of clinical and experimental evidence suggest that human herpesvirus 6 (HHV-6), particularly its A variant (HHV-6A), acts as an accelerating factor in HIV-1 disease [7]. In vitro, HHV-6A was shown to: i) replicate primarily in CD4 + T cells and cause their destruction in synergy with HIV-1 [8]; ii) transactivate the HIV-1 long terminal repeat [9]; iii) induce de novo CD4 expression and HIV-1 susceptibility in otherwise HIV-refractory cells such as CD8 + T lymphocytes and NK cells [10,11]; and iv) augment the release of HIV-1-enhancing inflammatory cytokines [12]. In vivo studies have documented: i) widespread HHV-6 infection in patients with full-blown AIDS at post-mortem examination [13,14]; ii) frequent reactivation of HHV-6 in early symptomatic HIV-1-infected subjects [15]; iii) vigorous HHV-6 replication in lymph nodes of HIV-1-infected subjects, associated with an increased local HIV-1 load [16,17]; and iv) accelerated progression of HIV-1 disease in infants who acquire HHV-6 within the first year of life [18].…”

Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1.

“…Dual infection of individual cells with HIV-1 and herpes viruses (12)(13)(14) or human T-lymphotropic virus type I (15) resulted in enhanced expression of HIV. Similarly, HIVinfected cells that were superinfected with or exposed to products of Mycobacterium tuberculosis (16) and Toxoplasma gondii (17) showed a significantly enhanced expression of HIV.…”