Human retrovirus expression in health and illness conditions: a possible role as a mediator of the inflammatory and immunopathogenic conditions

• Grant number: 23/08773-0
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2023 - October 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luiz Henrique da Silva Nali
• Grantee: Luiz Henrique da Silva Nali
• Host Institution: Universidade de Santo Amaro (UNISA). São Paulo , SP, Brazil
• Associated researchers: André Luis Lacerda Bachi ; Carolina Nunes França
• Associated scholarship(s): 24/05197-1 - Molecular, cellular and serological aspects associated with the role of Human Endogenous Retroviruses K and W in Autoimmune and Inflammatory Diseases and Health Conditions, BP.TT

Abstract

Human Endogenous Retroviruses (HERVs) are fossil retroviruses that infected germ cells of our ancestors millions of years ago. As with other retroviruses, the genome integration stage is characteristic of the viral replicative cycle. This resulted in integration into these germ cells and was a fundamental step in the endogenization process of the virus in the genome of our ancestors and its perpetuation through generations. During the evolution of our ancestors and hominids, these viruses were transmitted by retrotransposition, direct transmission and in a Mendelian way. Today, we know that 8% of the human genome is composed of HERV sequences. However, most of these viruses are defective (with the presence of mutations, presence of a stop codon in the coding region) and incomplete (partial genes or isolated LTRs). Despite their accumulated mutations, HERVs can be expressed, and the virion can be formed. Given this, it is plausible to understand that HERVs may play a role in human physiology or be an etiological mediator in some diseases, in particular, inflammatory or autoimmune diseases. In fact, physiological roles of HERVs have been described, such as thefusogenic role in formation of osteoclasts, skeletal striated muscle and syncytiotrophoblast for placental formation, and their LTRs may act by regulating nearby genes. On the other hand, HERVs may be associated with a number of autoimmune and inflammatory diseases. Although, important expression findings are being described mainly for Multiple Sclerosis, the involvement of this virus with other inflammatory or autoimmune diseases is still little explored, as well as the possible mechanism of induction of this autoimmunity. Thus, the objective of this study is to evaluate the expression dynamics of these HERVs in health and disease conditions. This will be an observational case-control study. To answer this question, blood samples from patients with the following diseases: Multiple Sclerosis, Chronic Venous Insufficiency and Vitiligo and healthy individuals will be collected and will compose the study groups. The evaluation of the expression of HERV-K and W in the groups will be through Real Time PCR with relative quantification by the 2-DDCt method. The concentration of serum pro and anti inflammatory cytokines will be determined by assay with commercial kits by ELISA. Monocyte, lymphocyte characterization and HERV protein expression in these cells will be determined by flow cytometry. Finally, the anti-HERV humoral response will be evaluated in the volunteers' serum by ELISA. (AU)