Carolina Scagnolari (Italy)
Sapienza Univeristy of Rome Molecular Medicine, Laboratory of VirologyPresenter of 1 Presentation
DECREASED IFN EPSILON EXPRESSION DURING HPV ANAL INFECTION IN HIV+ MEN (ID 773)
- Carolina Scagnolari (Italy)
- Letizia Santinelli (Italy)
- Fabiana Cannella (Italy)
- Mirko Scordio (Italy)
- Giuseppe Oliveto (Italy)
- Leonardo Sorrentino (Italy)
- Eugenio N. Cavallari (Italy)
- Gabriella D'Ettorre (Italy)
- Guido Antonelli (Italy)
- Paolo Gozzo (Italy)
- Raphael P. Viscidi (United States of America)
- Alessandra Pierangeli
Abstract
Introduction
Interferon (IFN)-epsilon is an emerging component of innate immune defence at the mucosal surface. HPV infection has been strongly associated with squamous cell carcinoma of the anal canal; its incidence is relatively low in the general population but substantially elevated in HIV-infected (HIV+) individuals. It remains to be understood whether anal HPV infection modulates the expression of IFN-epsilon. This study aims to characterize the mucosal expression of IFN-epsilon during anal HPV infection through an integrative analysis with common type I IFN components and virological parameters.
Methods
Anal brushings were collected from HIV+ men, attending Proctology and Infectious Disease Units at Policlinic Umberto I Hospital in Rome. Detection of HPV DNA and genotyping were performed by PCR and sequencing. The mRNA copy content of type I IFN-genes (alfa2, beta and epsilon) and their heterodimeric receptor IFNAR1-IFNAR2 was measured by TaqMan RT–PCR, relatively to a cellular invariant gene.
Results
This study included 50 Caucasian HIV+ patients on long-term antiretroviral therapy. HPV DNA was detected in 74% of anal samples and high-risk (HR) genotypes were more than half. Despite individual variability in expression levels, there was a strong positive correlation among IFN-epsilon, all type I IFN genes and IFNAR1 subunit. The expression levels of the type I IFN-genes were all lower in men positive to HR HPV-positive than in those positive to low-risk, consistently with what is known about cervical infections; interestingly, IFN-epsilon appeared more down-regulated than IFNs alfa2 and beta in the HR group.
Conclusions
In this first study on the type I IFNs response to HPV infection in the anal mucosa, IFN-epsilon expression appeared to be targeted by HR-HPVs. Follow-up studies will be performed to clarify the role of type I IFNs in anal HPV clearance and to ascertain local dysfunctions of mucosal immune response in HIV+ patients.