# Beyond Infection: The Role of Secreted Viral Proteins in Pathogenesis, Disease Severity and Diagnostic Applications

**Authors:** Luis Herrera-Moro Huitron, Víctor Javier Cruz-Holguin, José Manuel Ulloa-Aguilar, Luis Adrián De Jesús-González, Juan Fidel Osuna-Ramos, Mario Guzmán-Huerta, Mercedes Piedad de León-Bautista, Guadalupe León-Reyes, Julio García-Cordero, Leticia Cedillo-Barrón, Jorge Francisco Cerna-Cortes, Moisés León-Juárez

PMC · DOI: 10.3390/cells14090624 · 2025-04-22

## TL;DR

This paper reviews how secreted viral proteins influence disease severity, immune evasion, and diagnostic potential by altering host environments and signaling pathways.

## Contribution

The paper provides a comprehensive review of secreted viral proteins' roles in pathogenesis and their applications in diagnostics and therapies.

## Key findings

- Secreted viral proteins can suppress immune responses and promote disease progression.
- Examples like BARF1 and NS1 demonstrate their roles in cancer and early diagnosis.
- These proteins offer new targets for antiviral therapies and biosensing technologies.

## Abstract

Secreted viral proteins are crucial in virus–host interactions, as they modify the host microenvironment to promote infection. These secreted proteins could alter immune and inflammatory responses, allowing viruses to evade defense mechanisms such as cytotoxic T cell activation and antibody neutralization. Some secreted proteins mimic host molecules to suppress antiviral responses, making them valuable targets for antivirals and diagnostics. Notable examples include BARF1 from Epstein–Barr virus, associated with gastric cancer; vIL-10 from Epstein–Barr virus, which regulates immune responses and contributes to autoimmune diseases; NS1 from dengue virus, associated with vascular permeability and early diagnosis; and NSP4 from rotavirus as an enterotoxin, among others. The study of these proteins improves our understanding of viral pathogenesis and helps to develop innovative treatments for infectious and non-infectious diseases, taking advantage of the evolutionary adaptations of viruses. This review explores their impact on the infection cycle, disease progression, and key processes, such as cell cycle regulation, apoptosis, and cell signaling. Research on these proteins deepens our basic knowledge of virology and generates alternative methods for detecting biomarkers and creating more effective therapies, as well as implementing some emerging technologies, such as biosensors and plasmon resonance, for the diagnosis of viral diseases.

## Linked entities

- **Proteins:** BaRF1 (ribonucleotide reductase subunit 2), VILL (villin like), PTPN11 (protein tyrosine phosphatase non-receptor type 11), PRSS57 (serine protease 57)
- **Diseases:** gastric cancer (MONDO:0001056)

## Full-text entities

- **Genes:** BARF1 [NCBI Gene 17494226], IVNS1ABP (influenza virus NS1A binding protein) [NCBI Gene 10625] {aka ARA3, FLARA3, HSPC068, IMD70, KLHL39, ND1}
- **Diseases:** Infection (MESH:D007239), infectious diseases (MESH:D003141), autoimmune diseases (MESH:D001327), inflammatory (MESH:D007249), gastric cancer (MESH:D013274)
- **Species:** Rotavirus (genus) [taxon 10912], Dengue virus (no rank) [taxon 12637], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12071779/full.md

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Source: https://tomesphere.com/paper/PMC12071779