HIV-associated salivary gland disease: a review.

Human immunodeficiency virus-associated salivary gland disease (HIV-SGD) is defined as the presence of xerostomia and/or swelling of the major salivary glands. It is common among children but uncommon among adults. HIV-SGD includes lymphoepithelial lesions and cysts involving the salivary gland tissue and/or intraglandular lymph nodes, and Sj?gren's syndrome-like conditions, diffuse interstitial lymphocytosis syndrome, and other reported lesions of the major salivary glands. This article reviews the terminology, prevalence, symptoms, clinical features, diagnostic procedures, histopathology, serology, natural history, treatment, and pathogenesis of HIV-SGD.     

Salivary autoantibodies in HIV-associated salivary gland disease

A subset of HIV-positive patients develops salivary gland disease (HIV-SGD), characterized by salivary gland enlargement and/or decreased salivary flow. While clinical symptoms are similar to Sjögren's syndrome (SS). patients with HIV-SGD lack circulating anti-SS-A/Ro and anti-SS-B La. Occasionally, SS patients lacking circulating anti-SS-A/Ro and anti-SS-B'La have these antibodies in their saliva. Salivas from II patients with HIV-SGD, 13 HIV+ patients without HIV-SGD, 14 HIV-negative men controls, and 11 patients with SS were screened for autoantibodies. Five HIV-SGD salivas had antibodies recognizing the cytoplasm of a salivary cell line. No HIV 4- controls showed reactivity. Ten of 11 SS patients had salivary autoantibodies, and one HIV-negative control was positive for them. Salivary anti-SS-A/Ro was present in 8/11 SS patients, and 7 also contained anti-SS-B/La. No HIV-SGD salivary samples had these specific autoantibodies. These findings suggest that while glandular polyclonal expansion occurs in both HIV-SGD and SS, different autoantibodies are produced.     

Oral mucosal immunity and HIV/SIV infection

Human Immunodeficiency Virus (HIV) transmission through genital and rectal mucosa has led to intensive study of mucosal immune responses to HIV and to the development of a vaccine administered locally. However, HIV transmission through the oral mucosa is a rare event. The oral mucosa represents a physical barrier and contains immunological elements to prevent the invasion of pathogenic organisms. This particular defense differs between micro-compartments represented by the salivary glands, oral mucosa, and palatine tonsils. Secretory immunity of the salivary glands, unique features of cellular structure in the oral mucosa and palatine tonsils, the high rate of oral blood flow, and innate factors in saliva may all contribute to the resistance to HIV/Simian Immunodeficiency Virus (SIV) oral mucosal infection. In the early stage of HIV infection, humoral and cellular immunity and innate immune functions in oral mucosa are maintained. However, these particular immune responses may all be impaired as a result of chronic HIV infection. A better understanding of oral mucosal immune mechanisms should lead to improved prevention of viral and bacterial infections, particularly in immunocompromised persons with Acquired Immune Deficiency Syndrome (AIDS), and to the development of a novel strategy for a mucosal AIDS vaccine, as well as vaccines to combat other oral diseases, such as dental caries and periodontal diseases.     

Modulation of herpes simplex virus type 1 replication by human salivary secretions

Saliva functions to protect the oral cavity from pathogenic invasion by modulating the ability of microbes to colonize the oral surfaces or limiting their growth and/or viability. Although the role of salivary secretions in the modulation of the oral bacteria flora has received considerable attention, little is known concerning its role in viral pathogenesis. Accordingly, the purpose of this study was to assess the effect of salivary secretions on herpes simplex virus type 1 (HSV-1) replication. Initially, HSV-1 plaque and liter reduction assays were performed to determine the ability of human submandibular/sublingual (HSMSL) and parotid (HPS) salivas to inhibit the early stages of HSV-1 infection (adsorption and penetration). Our results suggested that both HSMSL and HPS possess cell-protective and virus neutralization activities, with HSMSL being more active than HPS. Additional experiments were performed to determine the effect of saliva on the yield of virus progeny. Again, HSMSL caused a greater reduction of HSV-1 replication than did HPS. A similar effect could not be obtained using vaccinia, suggesting that this inhibitory activity of human saliva is selective. Collectively, these results suggest that human salivary secretions can modulate the replication of HSV-I in vitro.     

Salivary gland involvement in HIV-1 infection.

After infection with human immunodeficiency virus (HIV)-1, virus can be recovered from both whole saliva (the total fluid contents of the mouth) and individual major salivary gland secretions. The concentration of virus is low, and recovery is infrequent. Antibodies (primarily of the IgA class) to HIV-1 are found in saliva. Despite the presence of virus, the oral cavity does not appear to be a route of transmission for HIV-1. This may relate to protective properties of saliva. It has been reported that whole saliva and mixed submandibular/sublingual secretions inhibit the infectivity of the virus in vitro. HIV infection also induces alterations in salivary gland function. Both salivary output and composition may be affected.     

(C2) Saliva, breast milk, and mucosal fluids in HIV transmission

The oral environment has received various amounts of attention in association with HIV infection and pathogenesis. Since HIV infection occurs through mucosal tissue, oral factors-including tissue, fluids, and compartments-are of interest in furthering our understanding of the diagnosis, infectivity, transmission, and pathogenesis of disease. This report reviews: (1) HIV testing and diagnoses with oral fluids; (2) post-natal acquisition of HIV in association with breast-feeding from HIV-positive mothers; and (3) oral sex and HIV transmission. In the first, we examine how oral fluids are used to detect HIV infection and review current consensus on the role of salivary molecules as markers for immunosuppression. Second, lactation-associated HIV acquisition is reviewed, with special consideration of emerging issues associated with the impact of anti-retroviral therapies. Last, we consider current data on the risk of HIV infection in association with oral sex. Investigation of these diverse topics has a common goal: understanding how HIV presents in the oral environment, with an aim to rapid and accessible HIV diagnosis, and improved prevention and treatment of infection.     

Gene transfer mediated by different viral vectors following direct cannulation of mouse submandibular salivary glands

The salivary gland has been suggested as an accessible organ for gene transfer to express recombinant proteins locally in the saliva, as well as for secretion to the blood circulation. The aim of this study was to evaluate the efficiency of gene transfer to salivary glands using different viral vectors: adenovirus, vaccinia, herpes simplex type 1 (HSV), and two retroviral vectors (murine leukemia virus (MuLV) and lentivirus). We show, by in situ staining and beta-galactosidase reporter activity assay, that the adenoviral and vaccinia vectors were able to deliver the reporter gene efficiently to acinar and duct cells. The HSV vector was less efficient and infected only the acinar cells. The lentiviral vector infected acinar and duct cells, but at a relatively low efficiency. The MuLV vector did not infect the salivary gland unless cell proliferation was induced. Host immune responses to viral infection, inflammation, apoptosis and lymphocyte infiltration, in the transduced glands, were assessed. The DNA viral vectors induced local lymphocyte infiltration and apoptosis. In contrast, the retroviral vectors did not induce an immune response. Our results describe the outcome of salivary gland infection with each of the five different viral vectors and indicate their advantages and limitations for transferring genes to the salivary glands.     

Salivary gland disorders: A comprehensive review

Salivary glands are complex in nature. They could be either tubulo acinar, merocrine or exocrine glands secreting mainly saliva. Salivary gland is one of the main soft tissue structures in the maxillofacial area. Saliva is a clear, slightly acidic muco serous fluid that coats the teeth, mucosa and thereby helps to create and maintain a healthy environment in the oral cavity. Salivary glands may be affected by a number of diseases: local and systemic and the prevalence of salivary gland diseases depend on various etiological factors. The glands may be infected by viral, bacterial, rarely fungal or its ductal obstruction which may cause painful swelling or obstruction, affecting their functions. The salivary gland may also be affected by a various benign and malignant tumours. This review article briefly describes about the various salivary gland disorders, diagnostic techniques and their management including the recent advances and the future perspective.     

Focused review of investigation,management and outcomes of salivary gland disease in specialty-specific journals

We review papers on diseases of the salivary glands published in journals relating to the head and neck, which are commonly read by members of our specialty. Most of the papers focus on the investigation and treatment of diseases of the parotid gland, which reflects the relative prevalence of parotid lesions among salivary gland diseases. Minimally invasive surgery is increasingly of interest. There is a lack of clinical trials that address the many controversies concerning salivary gland surgery, and much of the evidence for treatment is based on small case series and expert opinion, partly because of the relative rarity of salivary disease and the disparate groups that treat it. This problem could be addressed if regional and national oral and maxillofacial surgery (OMFS) units, and possibly other specialties, could collaborate more closely and combine data.     

Multiple components contribute to ability of saliva to inhibit influenza viruses

Introduction:  Saliva is a potentially important barrier against respiratory viral infection but its mechanism of action is not well studied.
Methods:  We tested the antiviral activities of whole saliva, specific salivary gland secretions, and purified salivary proteins against strains of influenza A virus (IAV) in vitro .
Results:  Whole saliva or parotid or submandibular/sublingual secretions from healthy donors inhibited IAV based on hemagglutination inhibition and neutralization assays. This differs from human immunodeficiency virus (HIV), for which only submandibular/sublingual secretions are reported to be inhibitory. Among purified salivary proteins, MUC5B, scavenger receptor cysteine-rich glycoprotein 340 (salivary gp-340), histatins, and human neutrophil defensins (HNPs) inhibited IAV at the concentrations present in whole saliva. In contrast, some abundant salivary proteins (acidic proline-rich proteins and amylase) had no activity, nor did several other less abundant salivary proteins with known activity against HIV (e.g. thrombospondin or serum leukocyte protease inhibitor). Whole saliva and MUC5B did not inhibit neuraminidase activity of IAV and viral neutralizing and aggregating activity of MUC5B was potentiated by the neuraminidase inhibitor oseltamivir. Hence, MUC5B inhibits IAV by presenting a sialic acid ligand for the viral hemagglutinin. The mechanism of action of histatins requires further study.
Conclusions:  These findings indicate that saliva represents an important initial barrier to IAV infection and underline the complexity of host defense activity of oral secretions. Of interest, antiviral activity of saliva against IAV and HIV differs in terms of specific glandular secretions and proteins that are inhibitory.     

与人类免疫缺陷病毒感染和艾滋病相关的口腔疾病的研究进展

艾滋病（AIDS）在口腔的表现是艾滋病诊断的重要指标之一。多数人类免疫缺陷病毒（HIV）感染患者都有口腔表现，但口腔表现却往往被忽视。目前与HIV感染密切相关的主要口腔疾病有口腔黏膜病、牙周病、涎腺疾病及龋病等。本文对HIV感染和艾滋病相关的口腔疾病的研究进展作一综述。     

Statherin levels in saliva of patients with precancerous and cancerous lesions of the oral cavity: a preliminary report

OBJECTIVE: The aim of this study was to measure concentration of human salivary statherin in patients with oral cavity pathologies and salivary gland diseases. SUBJECTS AND METHODS: Levels of statherin were analysed with High Performance Liquid Chromatography (HPLC) in following groups of subjects: group A: 24 patients with neoplastic diseases of salivary glands, group B: 13 patients with inflammatory lesions of salivary glands, group C: 13 patients with precancerous and cancerous lesions of the oral cavity excluding salivary gland tumors, group D: 20 healthy volunteers (control group). RESULTS: Our preliminary data indicated a sensible reduction of the statherin level in the saliva of patients with precancerous and cancerous lesions of the oral cavity (group C) compared with the healthy subjects (group D). The statherin levels are not significantly reduced either in the inflammatory (group B) or in the salivary glands tumours (group A), compared with the healthy subjects (group D). CONCLUSION: Statherin could play a protective effect in oral cavity in association with its other functions.     

Periodontal disease in HIV/AIDS

Since the early 1990's, the death rate from AIDS among adults has declined in most developed countries, largely because of newer antiretroviral therapies and improved access to these therapies. In addition, from 2006 to 2011, the total number of new cases of HIV infection worldwide has declined somewhat and has remained relatively constant. Nevertheless, because of the large numbers of existing and new cases of HIV infection, the dental practitioner and other healthcare practitioners will still be required to treat oral and periodontal conditions unique to HIV/AIDS as well as conventional periodontal diseases in HIV-infected adults and children. The oral and periodontal conditions most closely associated with HIV infection include oral candidiasis, oral hairy leukoplakia, Kaposi's sarcoma, salivary gland diseases, oral warts, other oral viral infections, linear gingival erythema and necrotizing gingival and periodontal diseases. While the incidence and prevalence of these oral lesions and conditions appear to be declining, in part because of antiretroviral therapy, dental and healthcare practitioners will need to continue to diagnose and treat the more conventional periodontal diseases in these HIV-infected populations. Finding low-cost and easily accessible and acceptable diagnostic and treatment approaches for both the microbiological and the inflammatory aspects of periodontal diseases in these populations are of particular importance, as the systemic spread of the local microbiota and inflammatory products of periodontal diseases may have adverse effects on both the progression of HIV infection and the effectiveness of antiretroviral therapy approaches. Developing and assessing low-cost and accessible diagnostic and treatment approaches to periodontal diseases, particularly in developing countries, will require an internationally coordinated effort to design and conduct standardized clinical trials.     

Saliva and inhibition of HIV-1 infection: molecular mechanisms

Oral fluids are rarely a vehicle for HIV-1 infection in vivo , unlike other mucosal secretions. This unique property raises questions regarding (1) the molecular mechanisms responsible for the lack of salivary transmission, (2) the extent to which oral immunological responses mirror responses at other mucosal sites, (3) the use of promising salivary markers of HIV-1 disease progression, (4) the relationship between oral and blood viral loads, (5) cofactors that influence oro-genital transmission, and (6) the feasibility of oral-based antibody testing for HIV-1 diagnosis in the home. This paper discusses these questions and provides background summaries, findings from new studies, consensus opinions, practical relevance to developing countries, and suggestions for future research agenda on each of the key topics.     

Study of oral changes in patients with eating disorders

Abstract: Background: The prevalence of eating disorders is very high in industrialized countries, especially in young women. The principal orodental manifestations are erosion of the dental enamel, caries and dental sensitivity. Objectives: Our aim was to study oral complications in female with eating disorders. Methods: We study oral complications (dental, mucosal and salivary) in 17 female patients from the Hospitalized Patients Eating Disorders Unit. Results: We found alterations in salivary flow and pH, as well as salivary gland enlargement. Conclusions: A significant alteration in oral tissue occurs; this has an adverse impact on oral health, producing an accumulation of local irritants which favour the appearance of oral diseases. Preventative measures are therefore recommended for this group of patients.     

Recent advances in the management of salivary gland disease

The management of salivary gland disease forms a considerable part of the work done by oral and maxillofacial surgeons. Fast track and one-stop head and neck lump clinics allow for early diagnosis of salivary gland tumours in most units, the emphasis being on outcome after operation for benign disease. There have been limited advances in salivary gland surgery in recent years. Most recent publications have compared outcome of new methods of treatment with conventional techniques. This article reviews papers related to diseases of the salivary glands published in the British Journal of Oral and Maxillofacial Surgery (BJOMS) over a two-year period (2007–2008), and includes other relevant articles to bring readers up to date about salivary gland disease.     

Salivary secretion in health and disease

Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.     

Human herpesvirus 6 in oral fluids from healthy individuals

Background: Human herpesvirus 6 (HHV6) is the etiologic agent of exanthem subitum. The virus is latent in salivary glands and saliva is the main form of viral transmission. The objective of this study was to assess HHV6 incidence in the fluids from healthy individuals using a standardised technique for collecting and extracting viral DNA from gingival crevicular fluid, whole saliva and parotid gland saliva.

Design: Samples of oral fluids and peripheral blood were collected from 28 blood donors and HHV6 was detected using PCR assay. Parotid gland saliva and gingival crevicular fluid were collected by endodontic paper cones in order to not contaminate these fluids with whole saliva.

Results: Of the 28 donors, 20 (71.4%) presented positive results in at least one of the three oral fluids researched. Whole saliva was positive in 19 (67.8%) volunteers, while only four (14.2%) samples of gingival crevicular fluid and four of parotid gland saliva proved to be positive.

Conclusions: The results suggest that HHV6 is present in the saliva of a large proportion of the healthy adult population. The use of endodontic paper cones for oral fluid collection and viral extraction was efficient, simple, cheap and painless. In spite of, the small number of cases studied it was possible to demonstrate that neither gingival crevicular fluid nor parotid gland saliva were the principal source of HHV6 in whole saliva.     

Viruses and oral diseases in HIV‐infected individuals on long‐term antiretroviral therapy: What are the risks and what are the mechanisms?

As a result of the extension of life span produced by increasing access to combined antiretroviral therapy, people living with HIV/AIDS (PLWH) face new challenges from comorbidities. Although advances in medical care for HIV infection have dramatically reduced opportunistic infections and AIDS‐defining cancers, some non‐AIDS‐defining cancers (NADC) and specific oral diseases such as periodontitis and salivary gland disease are now more prevalent. Cancer prevention is, therefore, a priority issue in care of PLWH, stressing both restoration of immune function and reduction of non‐HIV cancer risk factors (tobacco in all its forms; areca nut; heavy alcohol consumption; diets lacking antioxidant vitamins and minerals; and oncogenic virus infections) through specific interventions, especially tobacco and areca nut cessation and alcohol moderation. Detection of oral high‐risk human papillomaviruses (HR‐HPV) and the universal preventive HPV vaccination among PLWH should be promoted to reduce the malignancy burden, along with routine oral examinations which remain the cheapest, most reliable, most reproducible, and non‐invasive tool to identify suspicious lesions. Also, considerations of oral inflammation and periodontal health are important to replication and gene expression of viruses in the mouth. Considering that a key risk factor for this scenario is the presence of oncogenic virus infection such as several members of the human herpesvirus and human papillomavirus families, here we analyze the variables involved in the seeming increase in comorbidities in PLWH.     

Striated muscle involvement in experimental oral infection by herpes simplex virus type 1

Herpes simplex virus type 1 is one of the most frequent causes of oral infection in humans, especially during early childhood. Several experimental models have been developed to study the pathogenesis of this virus but all of them employed adult animals. In this work, we developed an experimental model that uses mice younger than 4 days old, to more closely resemble human infection. Mice were infected subcutaneously with the prototype strain McIntyre of Herpes simplex‐1, and the progression of infection was studied by immunoperoxidase. All animals died within 24–72 h post‐infection, while viral antigens were found in the oral epithelium, nerves and brain. The most striking result was the finding of viral antigens in the nucleus and cytoplasm of cells belonging to striated muscles. Organotypic cultures of striated muscles were performed, and viral replication was observed in them by immunocytochemistry, electron microscopy and viral isolation. We conclude that the infection of striated muscles is present from the onset of oral infection and, eventually, could explain some clinical observations in humans.