Unveiling the Crosstalk Between Endogenous Retroviruses and Nippostrongylus brasiliensis Infection: Implications for Host-Parasite Interactions

• Grant number: 25/14499-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: August 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Djalma de Souza Lima Júnior
• Grantee: Maria Luiza Vieira Félix
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/09270-2 - Decoding the role of endogenous retroviruses in controlling type 2 immunity, AP.JP

Abstract

Helminths are parasites that pose significant threats to human and animal health, affecting billions of individuals worldwide. Among them, Nippostrongylus brasiliensis has emerged as a valuable model organism for studying host-parasite interactions. While many studies have focused on understanding the immunological aspects of N. brasiliensis infection, the role of host endogenous elements, particularly endogenous retroviruses (ERVs), during helminth infections remains largely unexplored. ERVs are remnants of ancient retroviral infections that have integrated into the host genome and are transmitted vertically across generations. Recent evidence suggests that ERV reactivation can modulate host immune responses, yet their impact on parasitic infections is entirely unknown. Preliminary data from our group indicate that ERV reactivation promotes host immunity during helminth infection. We therefore hypothesize that helminth infection may trigger ERV reactivation, which in turn plays a critical role in host resistance to infection. In this context, the present proposal aims to investigate the role of ERV reactivation during N. brasiliensis infection by determining its involvement in the host immune response and its impact on disease pathogenesis. Understanding the ERV-helminth-host interaction may provide valuable insights into the molecular and immunological mechanisms underlying host-parasite interactions and uncover novel therapeutic targets for helminthic diseases. This study will employ a multidisciplinary approach combining epigenomics, transcriptomics, and immunological techniques to comprehensively examine the relationship between ERVs and helminth infections. By characterizing the landscape of endogenous retroviruses and analyzing their transcriptional activity during different stages of N. brasiliensis infection, we aim to identify specific retroviral elements potentially involved in modulating host immune responses. In addition, we will explore the functional significance of these retroviral elements through both in vitro and in vivo experiments, evaluating their impact on host immunity and susceptibility to N. brasiliensis infection. By elucidating the role of ERVs in N. brasiliensis infection, this research project not only advances our understanding of complex host-parasite interactions but also lays the groundwork for the development of new therapeutic strategies to combat helminth-associated diseases.