Despite the high prevalence of latent Kaposi's sarcoma-associated herpesvirus (KSHV) infections in patients from endemic areas with a high human immunodeficiency virus (HIV) prevalence, KSHV lytic reactivation in the context of other co-infections is not well understood. Lytic KSHV infections can contribute to severe inflammatory symptoms and KSHV-associated pathogenesis. We have previously reported on KSHV reactivation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure in a non-hospitalised cohort of people living with HIV (PLWH). From this cohort, we identified a 34-year-old male who presented for routine HIV care in May 2021 with an unusually high KSHV viral load (VL) of 189,946.3 copies/10 cells, before SARS-CoV-2 infection. The patient was invited into a 2-year follow-up study where his peripheral blood was analysed for selected virological, clinical, and inflammatory parameters every 6 months. He remained highly viremic for KSHV throughout the 2-year study period, during which he was infected with SARS-CoV-2 and developed disseminated tuberculosis, with steadily increasing levels of the inflammatory markers C-reactive protein (CRP), and interleukin-6 (IL-6). His HIV VL remained controlled (<1000 copies/mL) and his CD4 count bordered immunosuppression (±200 cells/µL), suggesting some responsiveness to antiretroviral treatment (ART). However, the patient's uncontrolled lytic KSHV infection may increase his risk for developing a KSHV-associated pathology manifesting with inflammation which should be closely monitored beyond the study period.
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http://dx.doi.org/10.3390/tropicalmed10020053 | DOI Listing |
Introduction: Kaposi's Sarcoma (KS) is a rare soft tissue tumor linked to human herpesvirus 8 (HHV-8), a recognized oncogenic virus. Five distinct clinical presentations have been identified, with the epidemic type being the most prevalent and notably associated with Human Immunodeficiency Virus (HIV). A delayed diagnosis significantly compromises patient prognosis and survival rates.
View Article and Find Full Text PDFPLoS Pathog
March 2025
Daniella Lee Casper Laboratory in Viral Oncology, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) is associated with several human malignancies. During latency, the viral genomes reside in the nucleus of infected cells as large non-integrated plasmids, known as episomes. To ensure episome maintenance, the latency protein LANA tethers the viral episomes to the cell chromosomes during cell division.
View Article and Find Full Text PDFCrit Rev Microbiol
March 2025
Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar, Odisha, India.
Infections account for approximately 15% of human cancers worldwide. Viruses are the most predominant infectious agents and can infect and alter various types of human cells thereby leading to the development of various forms of cancer. Current studies have reported that Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HBC), human papillomavirus (HPV), Kaposi's sarcoma-associated herpesvirus (KSHV), human T-lymphotropic virus 1 (HTLV-1), Markel cell polyomavirus (MCPyV), and BK polyomavirus are the most important oncogenic viruses that are directly involved in the initiation and progression of cancer.
View Article and Find Full Text PDFJ Virol
March 2025
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Unlabelled: Herpesviruses, including α-herpesvirus and herpes simplex virus (HSV-1), are masters of immune evasion. Previously we demonstrated that CD1d-restricted NKT cells are required for optimal anti-HSV-1 immune responses and HSV-1 efficiently downregulates CD1d to suppress NKT cell function. To delineate how the virus evades NKT cell function and establishes infection , we screened an HSV-1 expression library to identify the viral gene(s) downregulating CD1d and discovered that a leaky late gene, UL56, most efficiently suppresses CD1d expression by degrading the protein, apparently via both proteasome- and lysosome-dependent pathways.
View Article and Find Full Text PDFPLoS Pathog
March 2025
Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Cancer remains a leading cause of global mortality, characterized by high treatment costs, and generally poor prognoses. Developing new anti-cancer drugs requires substantial investment, extended development timelines, and a high failure rate. Therefore, repurposing existing US Food and Drug Administration (FDA)-approved drugs for other diseases as potential anti-cancer therapies offers a faster and more cost-effective approach.
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