Journal of Medical Virology Early Collection of Saliva Specimens from Bell’s Palsy Patients: Quantitative Analysis of HHV-6, HSV-1, and VZV Ombretta Turriziani, 1 * Francesca Falasca, 1 Paola Maida, 1 Aurelia Gaeta, 2 Corrado De Vito, 2 Patrizia Mancini, 3 Daniele De Seta, 3 Edoardo Covelli, 3 Giuseppe Attanasio, 3 and Guido Antonelli 1 1 Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy 2 Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy 3 Department of Sense Organs, Sapienza University of Rome, Rome, Italy Bell’s palsy is the most common cause of facial paralysis. Although it has been associated with diabetes mellitus, hypertension, pregnancy, and preeclampsia, the etiology of Bell’s palsy remains unknown. The reactivation of latent herpes sim- plex virus (HSV) or varicella-zoster virus (VZV) with subsequent inflammation and entrapment of the facial nerve in the narrow labyrinthine segment has been implicated as a cause of facial paralysis, but the active role of these viruses in Bell’s palsy is still discussed. This study quanti- fied HSV-1 DNA, VZV DNA, and HHV-6 DNA in 95 saliva samples collected from patients within 48 hr from the onset of paralysis. HSV-1, VZV, and HHV-6 were detected in 13%, 3%, and 61% of patients, respectively. The detection rate did not differ significantly between patients and a control group of healthy donors. Interestingly, however, the value of HHV-6 DNA copies was significantly higher than that detected in healthy donors. In addition, the mean value of HHV-6 DNA recorded in patients who had at least a one grade improvement of palsy at the first visit was significantly lower than that detected in patients who showed no change in facial palsy grade or an increase of at least one grade. These findings call into question the role of HSV-1 and VZV in the etiology of Bell’s palsy, and suggest that HHV-6 may be involved in the development of the disease or that the underlying disease mech- anism might predispose patients to HHV-6 reacti- vation. J. Med. Virol. # 2014 Wiley Periodicals, Inc. KEY WORDS: HSV1; HHV6; Bell’s palsy; VZV INTRODUCTION Bell’s palsy is an acute, generally unilateral, paral- ysis or weakness of facial musculature consistent with peripheral facial nerve dysfunction. The paraly- sis causes distortion of facial features and interferes with normal functions, such as closing the eye and eating. Bell’s palsy affects 11–40 people per 100,000 in the population per annum, most commonly in the age group 15–45 years [Yanagihara et al., 1988; Brandenberg and Annegers, 1993; Morris et al., 2002]. The prognosis is favorable, and approximately 70% of patients completely recover without treatment within 6 months. However, about 30% of Bell’s palsy patients have sequelae, such as residual paresis, contracture, and hemifacial spasm or synkinesis [Pietersen, 2002]. Moreover, significant sequelae have a long-term impact on patients’ quality of life, such as difficulty with drinking, eating and speaking, as well as psychosocial problems. Although Bell’s palsy has been associated with diabetes mellitus, hypertension, pregnancy, and pre- eclampsia [Pecket and Schattner, 1982; Yanagihara and Hyodo, 1988; Shmorgun et al., 2002], its etiology remains unknown. Viral infections, hereditary fac- tors, vascular ischemia, and autoimmunity have been postulated as probable causes of Bell’s palsy [Calca- terra et al., 1976; Thomsen and Barfoed, 1979; Greco et al., 2012]. More specifically, reactivation of herpes simplex virus type 1 (HSV-1) or varicella-zoster virus (VZV), with subsequent inflammation and entrap- ment of the facial nerve in the narrow labyrinthine segment, has been proposed to explain the mecha- nism of nerve injury [McCormick, 1972; Murakami et al., 1996; Furuta et al., 2000; Lackner et al., 2010].  Correspondence to: Ombretta Turriziani, Department of Molecular Medicine, Sapienza University of Rome, Viale dell’Universita ` 32, 00185 Rome, Italy. E-mail: ombretta.turriziani@uniroma1.it Accepted 7 February 2014 DOI 10.1002/jmv.23917 Published online in Wiley Online Library (wileyonlinelibrary.com).  C 2014 WILEY PERIODICALS, INC.