Effects of different radiation treatments on the human immunodeficiency virus-1 (HIV) promoter were reassessed for exposures comparable to those encountered in clinical or cosmetic practice, using survival of the host cell as a basis for comparisons. The exposures were performed with two ultraviolet radiation sources commonly used as medical or cosmetic devices (UVASUN 2000 and FS20 lamps), a germicidal (G15T8) lamp and an X-ray machine. The UVC component of the FS20 lamp was filtered out. The emission spectra of the lamps were determined. The characteristics of these sources allowed us to discriminate among effects of UVA1 (340-400 nm), UVB + UVA2 (280-340 nm) and UVC (254 nm) radiations. Effects of irradiation were ascertained using cultures of HeLa cells stably transfected with the HIV promoter linked to a reporter-chloramphenicol acetyl transferase-gene. The exposures used caused at least two logs of cell killing. In this cytotoxicity range, UVA1 or X radiations had no effect on the HIV promoter, whereas UVB + UVA2 or UVC radiations activated the HIV promoter in a fluence-dependent manner. Survivals following exposure to UVB + UVA2 or UVC radiation were (1) at the lowest measurable HIV promoter activation, 30 and 20%, respectively, (2) at one-half maximal activation, 6 and 3%, respectively and (3) at the maximal activation, 0.5 and 0.2%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Front Microbiol
January 2025
National Institute for Research in Tuberculosis, Indian Council of Medical Research, Chennai, India.
Pyrazinamide (PZA) is a key first-line antituberculosis drug that plays an important role in eradicating persister (TB) bacilli and shortening the duration of tuberculosis treatment. However, PZA-resistance is on the rise, particularly among persons with multidrug-resistant (MDR) tuberculosis. This nationwide study was conducted to explore the prevalence of mutations conferring PZA resistance, catalogue mutation diversity, investigate the associations of PZA resistance with specific lineages, examine co-resistance to 13 first- and second-line drugs, and evaluate the diagnostic accuracy of sequencing A and D genes for predicting PZA resistance.
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View Article and Find Full Text PDFJ Virol
January 2025
Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital Tübingen, Tübingen, Germany.
One key determinant of HIV-1 latency reversal is the activation of the viral long terminal repeat (LTR) by cellular transcription factors such as NF-κB and AP-1. Interestingly, the activity of these two transcription factors can be modulated by glucocorticoid receptors (GRs). Furthermore, the HIV-1 genome contains multiple binding sites for GRs.
View Article and Find Full Text PDFJ Virus Erad
December 2024
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.
View Article and Find Full Text PDFViruses
November 2024
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Robust CD8 T cell responses are critical for the control of HIV infection in both adults and children. Our understanding of the mechanisms driving these responses is based largely on studies of cells circulating in peripheral blood in adults, but the regulation of CD8 T cell responses in tissue sites is poorly understood, particularly in pediatric infections. DNA methylation is an epigenetic modification that regulates gene transcription.
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