Identification of viral protein R of human immunodeficiency virus-1 (HIV) and interleukin-6 as risk factors for malignancies in HIV-infected individuals: A cohort study

• Published in: PloS one Vol. 19; no. 1; p. e0296502
• Main Authors: Matsunaga, Akihiro, Ando, Naokatsu, Yamagata, Yuko, Shimura, Mari, Gatanaga, Hiroyuki, Oka, Shinichi, Ishizaka, Yukihito
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2024; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Analysis; Antibodies; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiviral agents; Biology and Life Sciences; Blood; Blood circulation; Cancer; Care and treatment; Cell cycle; Cervical cancer; Cytokines; Development and progression; DNA damage; Dosage and administration; Enzymes; Gastric cancer; Genotoxicity; Hepatitis B; Hepatitis C; Highly active antiretroviral therapy; HIV; HIV (Viruses); HIV infection; HIV patients; Human immunodeficiency virus; Immune system; Immunoassays; Immunoglobulin G; Infections; Inflammation; Interleukin 6; Interleukins; Lymphoma; Malignancy; Medical prognosis; Medicine and Health Sciences; Oxidative stress; Pancreatic cancer; Prevention; Prostate; Prostate cancer; Proteins; Regression analysis; Risk factors; Tumors; Viral proteins; Viruses; Vpr protein; Japan; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0296502

Despite effective antiretroviral therapy, patients with human immunodeficiency virus type-1 (HIV) suffer from a high frequency of malignancies, but related risk factors remain elusive. Here, we focused on blood-circulating viral protein R (Vpr) of HIV, which induces proinflammatory cytokine production and genotoxicity by exogenous functions. A total 404 blood samples of HIV patients comprising of 126 patients with malignancies (tumor group) and 278 patients without malignancies (non-tumor group), each of 96 samples was first selected by one-to-one propensity score matching. By a detergent-free enzyme-linked immunosorbent assays (detection limit, 3.9 ng/mL), we detected Vpr at a higher frequency in the matched tumor group (56.3%) than in the matched non-tumor group (39.6%) (P = 0.030), although there was no different distribution of Vpr levels (P = 0.372). We also detected anti-Vpr immunoglobulin (IgG), less frequently in the tumor group compared with the tumor group (22.9% for tumor group vs. 44.8% for non-tumor group, P = 0.002), and the proportion of patients positive for Vpr but negative of anti-Vpr IgG was significantly higher in the tumor group than in the non-tumor group (38.6% vs. 15.6%, respectively, P < 0.001). Additionally, Interleukin-6 (IL-6), the levels of which were high in HIV-1 infected patients (P < 0.001) compared to non-HIV-infected individuals, was significantly higher in advanced cases of tumors (P < 0.001), and IL-6 level was correlated with Vpr in the non-tumor group (P = 0.010). Finally, multivariate logistic regression analysis suggested a positive link of Vpr with tumor occurrence in HIV patients (P = 0.002). Vpr and IL-6 could be risk factors of HIV-1 associated malignancies, and it would be importance to monitor these molecules for well managing people living with HIV-1.