Carolina Scagnolari (Italy)

Sapienza Univeristy of Rome Molecular Medicine, Laboratory of Virology

Presenter of 1 Presentation

DECREASED IFN EPSILON EXPRESSION DURING HPV ANAL INFECTION IN HIV+ MEN (ID 773)

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.

Hide