# Viral Fragments in the Urine Proteome: New Clues to the Cause of Fever

## TL;DR

This study shows that viral fragments in urine can help identify the cause of unexplained fevers, offering a new diagnostic tool for doctors.

## Contribution

The study introduces a novel method using urinary proteomics to detect viral fragments in febrile patients without prior assumptions about the virus type.

## Key findings

- Viral fragments in urine were detected at much higher levels in febrile patients compared to healthy individuals.
- Specific viral peptides from multiple viruses, including monkeypox and influenza, were identified in urine samples.
- Salivirus A showed an increase of over 4200 times in febrile patients compared to controls.

## Abstract

Among the numerous causes of fever, accurately identifying the underlying etiology is essential for guiding clinical decisions. This study aimed to search for diagnostic clues for patients with fever of unknown origin by analyzing urinary proteins. The researchers collected urine samples from febrile patients and healthy individuals and detected viral fragments in them using liquid chromatography–tandem mass spectrometry technology. The results show that the detection levels of multiple viruses in the urine of febrile patients were much higher than those in healthy people. This indicates that viral fragments in urine can provide clues for investigating fever of unknown origin. In the future, it is expected to assist doctors in diagnosing fevers and other viral infectious diseases more quickly and accurately, thus safeguarding people’s health.

Background: To provide clues and a diagnostic basis for patients with fever of unknown origin through urinary proteomics analysis. Methods: For the first time, an attempt was made to conduct a full-library search for viruses in urine samples. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) technology was employed to analyze the urinary proteomes of patients with fever of unknown origin, and to search for and identify viral protein fragments. In this study, there is no need to pre-determine the types of substances present in the samples. As long as the relevant sequences of viruses are available in the database, virus searches can be performed on the samples. Results: In the urine samples, multiple specific peptides from various viruses, such as the monkeypox virus, salivirus A, human herpesvirus 8 type P, Middle East respiratory syndrome-related coronavirus, rotavirus A, Orf virus (strain NZ2), human herpesvirus 2 (strain HG52), human adenovirus E serotype 4, influenza A virus, human coronavirus NL63, parainfluenza virus 5 (strain W3), Nipah virus, and hepatitis C virus genotype 2k (isolate VAT96), could be observed. It was found that the detection amounts of multiple viruses in febrile patients were much higher than those in the control group. Among them, the increase multiple of salivirus A was as high as more than 4200 times, and the increase multiples of multiple viral proteins were higher than 20 times. Conclusions: Viral fragments in urinary proteins can be reliably identified using mass spectrometry, which provides clues for the investigation of unexplained fever and may also be applied to the exploration of any unknown diseases.