Related Experiment Video
Updated: Jul 11, 2025
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis
Gianluca Moroncini1, Silvia Svegliati2, Antonella Grieco2
1Università Politecnica delle Marche and Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy.
Objective:
The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex.
Methods:
The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc.
Results:
AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls.
Conclusion:
These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.
Insights
This study found adeno-associated virus type 5 (AAV5) in systemic sclerosis (SSc) lungs, forming a complex with platelet-derived growth factor receptor alpha (PDGFRα). This complex may trigger immune responses, offering a new insight into SSc pathogenesis.
Area of Science:
- Immunology
- Virology
- Pulmonology
Background:
- Systemic sclerosis (SSc) pathogenesis remains unknown.
- Platelet-derived growth factor receptors (PDGFRs) are overexpressed in SSc patients.
- PDGFRα is a target of adeno-associated virus type 5 (AAV5).
Purpose of the Study:
- To investigate if AAV5 forms a complex with PDGFRα.
- To determine if this complex exposes epitopes that induce immune responses in SSc.
Main Methods:
- In silico molecular docking and surface plasmon resonance (SPR) analyzed PDGFRα-AAV5 binding.
- AAV5 presence in SSc lungs was assessed using in situ hybridization and immunohistochemistry.
- Immune responses were evaluated using SSc patient antibodies and SPR.
Main Results:
- AAV5 was detected in the bronchoalveolar lavage (BAL) fluid of 62.1% of SSc patients versus 25.75% of controls.
- A molecular complex of AAV5 and PDGFRα with spatially contiguous epitopes was identified.
- SSc patient antibodies recognized epitopes from both PDGFRα and AAV5 within the complex.
Conclusions:
- AAV5 is linked to immune reactivity against endogenous antigens in SSc.
- The AAV5-PDGFRα complex represents a novel factor in SSc pathogenesis.
Related Concept Videos
00:42Cross-reactivity
01:25Immunodeficiency Diseases
There are three main causes of immunodeficiency...
01:26Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...