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9/26/2014  |   4:30 PM - 6:00 PM   |  

Salivary glands and human congenital cytomegalovirus infection: what happens in early fetal life?

Salivary glands are a privileged site of human cytomegalovirus (CMV) replication, latency and persistence. Prolonged viral secretion in saliva for months following a primary infection contribute to horizontal transmission. In order to understand the early effects of CMV on salivary glands and the mechanisms of viral persistent replication, we studied submandibular glands of 10 fetuses at 21 weeks gestation with CMV congenital infection. As negative controls, we studied four fetuses at the same gestational age from CMV-seronegative women. We performed immunohistochemistry for Gross Cystic Disease Fluid Protein (GCDFP)-15 and lysozyme to analyze the secretory proteins of the saliva, for CD4, CD8, CD20, Granzyme B to investigate inflammatory infiltrate, for p63 to study myoepithelial cells, for Ki67 to evaluate cellular proliferation. Development and branching of salivary glands were evaluated by counting the number of terminal acini. Submandibular glands from CMV infected fetuses showed a marked reduction in branching and formation of terminal acini compared to controls. Inflammatory infiltrate was present in CMV-positive glands, mainly composed of T CD8 cytotoxic lymphocytes, sometimes activated. In negative controls, GCDFP-15 and lysozyme were present in ducts and terminal units along the apical membrane border and in the lumen. In CMV fetuses, their expression was mainly observed as granular material in the cytoplasm of upper pole of the epithelial cells. Myoepithelial cells were observed in controls as a continuous sub-epithelial layer along ducts and acinar structures. In CMV fetuses, p63 positive-cells were markedly reduced, especially in the terminal units, and found as a discontinuous sub-epithelial layer. Cellular proliferation was found to be high in controls and low in infected fetuses. Our findings suggest that CMV may affect the glands early in gestation, with abnormal branching and reduced acinar structures. CMV may also alter the secretory cycle of proteins involved in the umoral defense favoring viral persistence.

Liliana Gabrielli (Primary Presenter), liliana.gabrielli@aosp.bo.it;
She graduated with a degree in Medicine and Surgery from the University of Bologna (Italy). She is Medical Doctor, Specialist in Microbiology and Virology, Consultant at University Hospital of Bologna, St. Orsola Malpighi General Hospital. She works at the Clinical Operative of Microbiology, Laboratory of Virology. Since her thesis she has published more than 50 scientific papers (31 on international-selected Current Contents and 19 on national and international journals). Visiting Professor in 2000 at the Department of Medical Virology, University Hospital of Tubingen, Germany and the Department of Virology, University of Ulm, Germany to investigate some aspects of the mechanism of pathogenesis of congenital cytomegalovirus infection. Degree Honors and Awards: “AMCLI”, Italian Society for Clinical Microbiology (2000 and 2007) and “Eva contro Eva – tra biologia e società”, Italian Society of Gynaecology and Obstetrics (SIGO) (2005).

ASHA DISCLOSURE:

Financial - No relevant financial relationship exist.

Nonfinancial - No relevant nonfinancial relationship exist.

Maria Paola Bonasoni (Author), bonasoni.mariapaola@asmn.re.it;
She graduated with a degree in Medicine and Surgery from the University of Bologna (Italy). She is Medical Doctor, Specialist in Pathology at the University of Bologna (Italy). She works at the Operative Unit of Pathology, St. Maria Nuova Hospital, Reggio Emilia, Italy.

Giulia Piccirilli (Author), giulia.piccirilli@yahoo.it;
She graduated with a degree in Biological Science from the University of Bologna (Italy) and she is receiving her scientific training for her specialty degree in Microbiology and Virology at the University of Bologna (Italy). She works at the Clinical Operative of Microbiology at St. Orsola Malpighi University General Hospital, Bologna (Italy).

Angela Chiereghin (Author), angela.chiereghin@gmail.com;
She graduated with a degree in Biological Science from the University of Bologna (Italy) and received her scientific training for her specialty degree in Microbiology and Virology at the University of Bologna (Italy). She works at the Clinical Operative of Microbiology at St. Orsola Malpighi University General Hospital, Bologna (Italy). PhD in Medical Sciences.

Tiziana Lazzarotto (Author), tiziana.lazzarotto@unibo.it;
She graduated with a degree in Biological Science from the University of Bologna (Italy) and received her scientific training for her specialty degree in Microbiology and Virology at the University of Bologna (Italy). She is Associate Professor of Microbiology and Clinical Microbiology, Department of Specialised, Experimental and Diagnostic Medicine, School of Medicine at Alma Mater Studiorum University of Bologna (Italy). Head of the Laboratory of Virology at the Clinical Operative of Microbiology at St. Orsola Malpighi University General Hospital, Bologna (Italy). Since her thesis she has published more than 168 scientific papers (121 on international-selected Current Contents, and 47 on national and international journals). In particular she has made significant contributions in the diagnosis and prognosis of congenital cytomegalovirus infection. Visiting Professor in 2000 at the Department of Paediatrics, University of Alabama, Birmingham, USA.

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