Oral Health Group
Feature

Oral Clinical Manifestations of Patients Infected with Zika Virus


December 2, 2016
by Walter L. Siqueira; David Zuanazzi; Zohaib Khurshid; Rabia Sannam Khan; Thais Marchini de Oliverira; Paula K. Jorge; Yuliya Mulyar; Maria Aparecida A. M. Machado

Few studies have described ZIKV manifestations in the mouth of infected patients. Recently, Brasil et al. reported local hyperemia and petechiae on the hard palate of an infected patient. 1 Some viruses are transmitted through saliva, including herpes simplex virus types 1 and 2 (HSV1, HSV2) and cytomegalovirus (CMV). 2 Notably, HSV and ZIKV display common characteristics, despite being from different families. They are both neurotropic viruses capable of infecting and replicating in neural cells. 3 Moreover, ZIKV, HSV2, and CMV are able to cross the placental membrane causing congenital microcephaly. 4 However, it is not known whether ZIKV can persist in a latent state and be reactivated like HSV, which causes recurrent ulceration of oral tissues including gingiva and oral mucosa. 5

In vitro, ZIKV exhibits the ability to infect and propagate in human skin cells including keratinocytes, fibroblasts, and immature dendritic cells. 6 Notably, all these cell types are present in the mouth. Therefore, it is possible that these cells are permissive to ZIKV infection and replication in oral tissues, as they share many characteristics with human skin cells, including expression of the AXL receptor. 6 AXL is responsible for the entry of ZIKV into fibroblasts and is also expressed in macrophages and vascular endothelial cells. 7

ZIKV RNA has been detected in saliva and persists for 29 days. 8 In theory, infection and replication in permissive endothelial cells of the gingiva and oral mucosa could permit entry of ZIKV into the mouth. From endothelial cells, ZIKV could invade the gingival/mucosal connective tissues, where the virus would infect and propagate in fibroblasts before reaching the epithelial keratinocytes. This route may explain the local hyperemia and petechiae observed by Brasil et al. 1 Another possible way for ZIKV to enter the mouth is by infecting the major and hundreds of minor salivary glands, including those in the hard palate, with subsequent release of viral particles in saliva as CMV, which is transmitted via saliva after infecting salivary glands where it maintains latency. 2 A third route may be via gingival crevicular fluid – an exudate from the gingival crevice surrounding the teeth.

Clearly, further studies are needed to investigate the oral manifestations of ZIKV in humans and its mechanism of entrance into the mouth. Saliva may play a critical role in human-to-human transmission of ZIKV and salivary diagnostics may provide a convenient point-of-care test for ZIKV infection. OH

Oral Health welcomes this original article.

References
1. Brasil P, Calvet GA, de Souza RV, Siqueira AM. Exanthema associated with Zika virus infection. Lancet Infect Dis 2016; 16(7): 866.
2. Balthesen M, Dreher L, Lucin P, Reddehase MJ. The establishment of cytomegalovirus latency in organs is not linked to local virus production during primary infection. J Gen Virol 1994; 75 ( Pt 9): 2329-36.
3. Cugola FR, Fernandes IR, Russo FB, et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature 2016; 534(7606): 267-71.
4. Baskin HJ, Hedlund G. Neuroimaging of herpesvirus infections in children. Pediatr Radiol 2007; 37(10): 949-63.
5. Steiner I, Kennedy PG, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 2007; 6(11): 1015-28.
6. Hamel R, Dejarnac O, Wichit S, et al. Biology of Zika Virus Infection in Human Skin Cells. J Virol 2015; 89(17): 8880-96.
7. Lemke G, Rothlin CV. Immunobiology of the TAM receptors. Nat Rev Immunol 2008; 8(5): 327-36.
8. Barzon L, Pacenti M, Berto A, et al. Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016. Euro Surveill 2016; 21(10).


About the Author
Walter L. Siqueira, David Zuanazzi, Paula K. Jorge, Yuliya Mulyar, School of Dentistry and Department of Biochemistry, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. Thais Marchini de Oliverira; Paula K. Jorge; Maria Aparecida A. M. Machado, Department of Pediatric Dentistry, Bauru Dental School, Bauru, Sao Paulo, Brazil. Zohaib Khurshid, College of Dentistry, King Faisal University, Saudi ArabiaRabia Sannam Khan, College of Dentistry, Baqai Univeristy, Pakistan.