UV activation of human immunodeficiency virus gene expression in transgenic mice

Abstract

Human immunodeficiency virus (HIV) infection is associated with a clinical latency of as long as 10 years before the development of disease. One explanation for this delay is the requirement of cofactors such as other DNA or RNA viruses, cytokines critical for immune modulation, or environmental UV light. At least in tissue culture studies, these agents are capable of inducing HIV gene expression in cell lines which either harbor the entire viral genome or contain a reporter gene under the control of the viral long terminal repeat regulatory region. The role of these cofactors in terminating clinical latency and inducing disease has been difficult to ascertain because of the lack of an appropriate animal model. We now report that UV light can markedly induce HIV gene expression in transgenic mice carrying both the cis-acting (long terminal repeat) and transacting (the tat gene) elements which are essential for viral transactivation and replication in infected cells. Our finding may explain the clinical observations that cutaneous lesions in HIV-infected individuals are often seen in the sunlight exposed areas of the skin, including the face and neck.

HIV, UV and immunosuppression

“…No effect was detected after UVA irradiation. Similar results were noted by Vogel et al (14), who showed that UVC, UVB and natural sunlight could induce HIV gene expression in transgenic mice carrying both HIV-LTR and the tat gene.…”

Activation of HIV in Human Skin by Ultraviolet B Radiation and its Inhibition by NFκB Blocking Agents¶

“…Concern about a detrimental relationship between ultraviolet radiation and HIV infection was triggered by cell culture (1)(2)(3)(4)(5)(6) and transgenic animal studies (7)(8)(9) that have shown ul- ¶Posted on the website on 17 traviolet B (UVB), ultraviolet C and psoralens plus ultraviolet A (PUVA) treatments to upregulate HIV gene expression, activate latent HIV or promote HIV replication (or all of them). Alerted by these findings, clinical investigators studied serial cases of HIV-infected patients treated for psoriasis, eosinophilic folliculitis or pruritus, with either UVB phototherapy or PUVA photochemotherapy (10)(11)(12)(13)(14)(15).…”

Is Phototherapy Safe for HIV‐Infected Individuals?

“…Based on the clearest evidence at hand, the dogmatic among us would say it is not safe. As cited, UVB and PUVA can activate HIV in vitro and in transgenic animals (5)(6)(7)(8)(9)(10)(11)(12). U1traviolet B can inhibit the immunological presentation of new antigens including components of infectious agents (3,16,17).…”

“…Support for the contention that UV radiation exerts deleterious effects on HIV infection derives principally from in vitro and transgenic animal experiments in which HIV markers were induced or upregulated (5)(6)(7)(8)(9)(10)(11)(12). These observations have led to the hypothesis that UV-induced cellular DNA damage stimulates DNA repair mechanisms, which, in turn, can activate transcription and replication of HIV (7).…”

“…The advent of the acquired immunodeficiency virus syndrome (AIDS) epidemic in the U.S. has focused even greater attention on phototherapy. Of concern is the high prevalence of unresponsive skin disorders associated with human immunodeficiency virus (HIV) infection and the ability of UV to suppress T cell-mediated immune responses (3.4 more importantly, UV has been shown to induce HIV activation and replication (5)(6)(7)(8)(9)(10)(11)(12). The purpose of this review is to lay out the evidence for and against the safety of UVB and PUVA therapy in HIV infection, to gauge the confidence level that we can attach to this evidence and to identify information (both existing and nonexisting) that might guide the use of UV therapy in HIV-related skin disease.…”