Induction of Expression of Human Immunodeficiency Virus in a Chronically Infected Promonocytic Cell Line by Ultraviolet Irradiation

Abstract

Infection with the human immunodeficiency virus (HIV) is often followed by a prolonged latent state, and mechanisms of maintaining latency or inducing expression from latency are active areas in AIDS research. It has been previously shown using a variety of viruses and cell systems that ultraviolet (UV) irradiation is capable of inducing the expression of latent viruses as well as augmenting the effects of acute viral infection. The ability of UV irradiation to affect HIV latency was investigated using a chronically HIV-infected, virus nonexpressing promonocytic cell line termed U1. After exposure to UV-C in doses ranging from 0.75 to 2.0 mJ/cm2, U1 cells were induced to express virus as assessed by detection of elevated reverse transcriptase activity and p24 antigen levels in culture supernatants of treated cells compared with unstimulated controls. In addition, immunofluorescence on cytospin preparations of UV-irradiated cells revealed a time-dependent increase in viral antigen production after UV stimulation. A similar increase in RT levels was seen after exposure of U1 cells to UV-B, although somewhat higher doses of UV-B (mJ) were required compared with UV-C (mJ). Viral induction by UV irradiation was associated with a drop in viability and a static growth curve, suggesting that a certain level of cellular stress was most likely necessary to initiate viral expression. The potential role of UV-induced cell damage with activation of a cellular "SOS" repair response is a probable explanation of the enhanced viral production observed.

Pathogenesis of Human Immunodeficiency Virus Infection

“…In other studies, halogenated pyrimidines, UV irradiation, and heat shock have led to virus activation (140,672,1125,1134), perhaps secondary to DNA damage (1210) (Fig. 10).…”

Combination of Biological Screening in a Cellular Model of Viral Latency and Virtual Screening Identifies Novel Compounds That Reactivate HIV-1

“…Another hypothesis we explored is that MMQO damages DNA and promotes the activation of cytokines or the ATM/ATR response that, through NF-B, could stimulate the HIV-1 promoter. It has been previously described that damaging agents such as UV light may induce the HIV-1 promoter (70,76). We ruled out the participation of ATM/ATR, as an inhibitor of this pathway does not block the stimulating effect of MMQO.…”

Activation of Human Immunodeficiency Virus by Ultraviolet Radiation

“…Z. Zmudzka, (unpublished) determined that the HIV promoter can be effectively activated in stably transfected HIVcat/HeLa cells by UVC and UVB, but not UVA radiation. Similarly, UVC and UVB, but not UVA, were found to induce virus expression in a promonocytic cell line chronically infected with HIV (Stanley et al, 1989).…”

“…Its latent form in a human T-cell line, which does not normally produce the virus, was activated by cell exposure to 5'-iododeoxyuridine (IUdR) (Folks et al, 1986). Stanley et al (1989) showed that HIV growth is activated in UVB or UVC irradiated U1 cells, which were chronically infected but supported only a low level of virus production. These authors found that exposures which produced killing of about 25% of the cells are required to produce maximal virus activation.…”

“…Generally, HIV activation and its promoter induction were observed following UVB or UVC exposures sufficient to kill 10-50% of cells (Valerie et al, 1988;Stanley et al, 1989; J. Z .…”