Oral Potentially Malignant Disorders and Candida in Oral Tongue Squamous Cell Carcinoma Patients.

This retrospective study addressed the role of oral potentially malignant disorders and the presence of intraepithelial Candida hyphae in the carcinogenesis of the oral tongue squamous cell carcinoma and its association with smoking, alcohol consumption, and oral inflammatory burden. The medical records of 183 subjects diagnosed with oral tongue squamous cell carcinoma at the Helsinki University Hospital were investigated. Preceding oral lichen planus, lichenoid reaction, and leukoplakia diagnosis were recorded. Further, the data on Candida hyphae in histological samples as an indicator of oral candidiasis, oral inflammatory burden, smoking, and alcohol consumption were recorded and analyzed. The histopathological diagnosis of oral lichen planus/lichenoid reaction (p < 0.001) and the presence of Candida hyphae (p = 0.005) were associated significantly with female gender. Oral lichen planus/lichenoid reaction patients were less often smokers than patients without these lesions. Candida hyphae were more often recorded in patients without alcohol use (p = 0.012). Oral lichen planus/lichenoid reaction and Candida hyphae in histological samples were associated with female gender and lower levels of typical risk factors, such as alcohol use and smoking, in oral tongue squamous cell carcinoma patients. Therefore, these patients should be well monitored despite a potential lack of the classical risk factors of oral carcinoma.

Home-Applied Dual-Light Photodynamic Therapy in the Treatment of Stable Chronic Periodontitis (HOPE-CP)-Three-Month Interim Results.

A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients were randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination was conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BOP) was lower in the NSPT + Lumoral®-group than in the NSPT group (p = 0.045), and more patients in the NSPT + Lumoral®-group had their BOP below 10% (54% vs. 22%, respectively, p = 0.008). In addition, patients in the NSPT + Lumoral®-group improved their oral hygiene by visible-plaque-index (p = 0.0003), while the NSPT group showed no statistical improvement compared to the baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT + Lumoral® group (92% vs. 63%, p = 0.02). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT + Lumoral®-group (71% vs. 33%, p = 0.01). Patients with initially less than ten deep pockets had fewer deep pockets at the three-month follow-up in the Lumoral® group (p = 0.01). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy.

Generalized infections of putative oral origin in Helsinki University Hospital in 2012 to 2017.

OBJECTIVE: Bacteria entering the bloodstream through oral mucosa cause bacteremia, which can lead to septic or distant infections. The underlying factors and need for dental treatment in patients referred for oral examination because of septic infection were investigated. It was expected that general diseases and poor socioeconomic status of patients would increase the risk of bacteremia. METHOD AND MATERIALS: This descriptive retrospective study included patients (N = 128) referred from medical clinics of the Helsinki University Hospital (HUH), during 2012 to 2017, to the Department of Oral and Maxillofacial Diseases due to bacteremia suspected to be of oral origin. Data were extracted from medical and dental records according to the World Health Organization International Classification of Diseases (ICD-10) for systemic or remote infections. Different groups were formed using modified Skapinakis classification for socioeconomic status (SES), from I (high) to V (low). Underlying medical conditions were retrieved according to McCabe classification: healthy, nonfatal, ultimately fatal, and rapidly fatal diseases. The data were analyzed using the statistical software package SPSS (IBM). RESULTS: Patients were referred most often from the Departments of Infectious Diseases and Internal Medicine. Because of infection, 12 patients needed aortic or mitral valve operations. Many of the patients were intravenous drug users. However, the majority of patients presented McCabe class I, indicating no systemic disease. The main SES was intermediate III. Tooth extraction was the principal mode of treatment. No demographic background variables were identified to explain increase of the risk for bacteremia except that most patients were men with untreated dental problems. CONCLUSIONS: Contrary to the authors' expectation, poor SES and underlying diseases did not seem to link to the outcome. However, untreated dental infections present an evident risk for life-threatening septic complications also in generally healthy individuals.

Triage and urgent dental care for COVID-19 patients in the Hospital District of Helsinki and Uusimaa.

OBJECTIVE: This paper describes and reports the patient-specific characteristics of an urgent dental care clinic for COVID-19 infected, suspected, exposed or quarantined patients from March to December 2020 in the Hospital District of Helsinki and Uusimaa, Finland. MATERIAL AND METHODS: The triage and the treatment protocol were established based on the scientific data. Patient files were evaluated from the hospital district's electronic medical record system. IBM SPSS software was used for statistical analysis. RESULTS: There were 1114 consultations and 257 visits at the clinic. Most of the patients were generally healthy with mean age of 35, had toothache and were suspected to be SARS-CoV-2 positive. Seventeen of the patients received positive tests for COVID-19 infection. The main treatment was tooth extraction, mostly due to caries. Statistically significant differences between COVID-19 infected and other patients occurred in age (45 vs 34 years-of-age, p = .009) and number of teeth (25 vs 28, p = .031). No SARS-CoV-2 infection transmission chains were traced to the clinic. CONCLUSION: During the challenging pandemic time, patients were carefully screened by specialists in clinical dentistry and treated safely and effectively. Patient-specific characteristics revealed no differences between COVID-19 infected and other patients in terms of symptoms or treatment needs.

Patients with autoimmune polyendocrine syndrome type 1 have an increased susceptibility to severe herpesvirus infections.

Almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) have neutralizing antibodies against type 1 interferons (IFN), important mediators of antiviral defense. Recently, neutralizing anti-IFN antibodies were shown to be a risk factor of severe COVID-19. Here we show in a cohort of 44 patients with APS-1 that higher titers of neutralizing anti-IFNα4 antibodies are associated with a higher and earlier incidence of VZV reactivation (herpes zoster). The patients also present with uncommonly severe clinical sequelae of herpetic infections. APS-1 patients had decreased humoral immune responses to varicella zoster virus, but cellular responses were comparable to healthy controls. These results suggest that blocking the type I interferon pathway in patients with APS-1 patients leads to a clinically significant immune deficiency, and susceptibility to herpesviruses should be taken into account when treating patients with APS-1.

Odontogenic causes complicating the chronic rhinosinusitis diagnosis.

OBJECTIVES: Chronic rhinosinusitis (CRS) frequently stems from a dental origin, although odontogenic sinusitis (OS) remains underdiagnosed amongst different professionals. This study aimed to explore how often odontogenic causes are considered when diagnosing CRS. MATERIALS AND METHODS: Patient records from 374 new CRS patients treated at a tertiary-level ear, nose, and throat (ENT) clinic were selected. Entries and radiological reports were assessed exploring how often dentition was mentioned and OS was suspected, how often radiologists reported maxillary teeth, and how commonly typical OS microbial findings and unilateral symptoms occurred. RESULTS: Although 10.1% of the CRS diagnoses were connected to possible dental issues, teeth were not mentioned for 73.8% of patients. Radiological reports were available from 267 computed or cone beam computed tomographies, of which 25.1% did not mention the maxillary teeth. The reported maxillary teeth pathology was not considered in 31/64 (48.4%) cases. Unilateral symptoms associated with apical periodontitis (OR = 2.49, 95% CI 1.27-4.89, p = 0.008). Microbial samples were available from 88 patients, for whom Staphylococcus aureus was the most common finding (17% of samples). CONCLUSIONS: Odontogenic causes are often overlooked when diagnosing CRS. To provide adequate treatment, routine assessment of patient's dental history and status, careful radiograph evaluation, and utilization of microbial findings should be performed. Close cooperation with dentists is mandatory. CLINICAL RELEVANCE: Dental professionals should be aware of difficulties medical professionals encounter when diagnosing possible OS. Thus, sufficient knowledge of OS pathology is essential to both medical and dental professionals.

HERQ-9 Is a New Multiplex PCR for Differentiation and Quantification of All Nine Human Herpesviruses.

Infections with the nine human herpesviruses (HHVs) are globally prevalent and characterized by lifelong persistence. Reactivations can potentially manifest as life-threatening conditions for which the demonstration of viral DNA is essential. In the present study, we developed HERQ-9, a pan-HHV quantitative PCR designed in triplex reactions to differentiate and quantify each of the HHV-DNAs: (i) herpes simplex viruses 1 and 2 and varicella-zoster virus; (ii) Epstein-Barr virus, human cytomegalovirus, and Kaposi's sarcoma-associated herpesvirus; and (iii) HHV-6A, -6B, and -7. The method was validated with prequantified reference standards as well as with mucocutaneous swabs and cerebrospinal fluid, plasma, and tonsillar tissue samples. Our findings highlight the value of multiplexing in the diagnosis of many unsuspected, yet clinically relevant, herpesviruses. In addition, we report here frequent HHV-DNA co-occurrences in clinical samples, including some previously unknown. HERQ-9 exhibited high specificity and sensitivity (LOD95s of ∼10 to ∼17 copies/reaction), with a dynamic range of 101 to 106 copies/µl. Moreover, it performed accurately in the coamplification of both high- and low-abundance targets in the same reaction. In conclusion, we demonstrated that HERQ-9 is suitable for the diagnosis of a plethora of herpesvirus-related diseases. Besides its significance to clinical management, the method is valuable for the assessment of hitherto-unexplored synergistic effects of herpesvirus coinfections. Furthermore, its high sensitivity enables studies on the human virome, often dealing with minute quantities of persisting HHVs.IMPORTANCE By adulthood, almost all humans become infected by at least one herpesvirus (HHV). The maladies inflicted by these microbes extend beyond the initial infection, as they remain inside our cells for life and can reactivate, causing severe diseases. The diagnosis of active infection by these ubiquitous pathogens includes the detection of DNA with sensitive and specific assays. We developed the first quantitative PCR assay (HERQ-9) designed to identify and quantify each of the nine human herpesviruses. The simultaneous detection of HHVs in the same sample is important since they may act together to induce life-threatening conditions. Moreover, the high sensitivity of our method is of extreme value for assessment of the effects of these viruses persisting in our body and their long-term consequences on our health.

Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study.

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (p<0.001) and older age (p<0.001). We also observed an inverse correlation between S-Amyl and S-CRP levels (AT, r = -0.519; PTA, r = -0.353). Therefore, we observed a group of PTA patients without signs of tonsillar infection who had significantly lower S-CRP levels than other PTA patients. These findings support that PTA may be caused by an etiology other than AT. Variations in the S-Amyl levels and a negative correlation between S-Amyl and S-CRP levels may indicate that minor salivary glands are involved in PTA development.

The relationship between oral diseases and infectious complications in patients under dialysis.

OBJECTIVES: Association was investigated between oral health before dialysis and the incidence of systemic infections during dialysis. We hypothesized that low-grade systemic inflammation caused by poor oral health associates with infectious episodes in patients on dialysis, despite earlier eradication of oral infection foci. SUBJECTS AND METHODS: A total of 117 patients (46 with peritoneal and 71 with hemodialysis) were examined and treated at predialysis stage and followed up during dialysis. Number of infection episodes and microorganisms cultured from blood and peritoneal fluid were analyzed. Number of teeth, periodontal inflammatory burden, and total dental index scores were assessed, and salivary matrix metalloproteinase 8, triggering receptor on myeloid cells 1, peptidoglycan recognition protein 1 (PGLYRP1), and interleukin-1ß were measured. RESULTS: In hemodialysis, 134 infection episodes were recorded, while peritoneal dialysis group had 77 peritonitis episodes. Culture-negative samples were 69% in hemodialysis and 23% in peritoneal dialysis group. Staphylococci were the most frequently associated microorganisms. Infections during dialysis did neither associate with oral health parameters nor associate with salivary inflammatory biomarkers, except for PGLYRP1, which associated with number of infection episodes during hemodialysis (p = .046). CONCLUSIONS: A number of infection episodes during hemodialysis were associated with salivary PGLYRP1 but not the other salivary markers or oral infection markers.

Acute rhinosinusitis - are we forgetting the possibility of a dental origin? A retrospective study of 385 patients.

Background: Odontogenic sinusitis (OS) is a common but underdiagnosed form of acute rhinosinusitis (ARS). OS carries no specific characteristics, but unilateral symptoms and certain microbiological as well as radiological findings indicate odontogenic origin. Aims/objectives: We studied the proportion of OS in ARS patients, the presence and associations of unilateral symptoms, and possible OS microbial and radiological findings. In addition, we investigated how this condition is recognised among ear, nose and throat specialists and radiologists. Materials and methods: All 676 ARS patients treated in the Department of Otorhinolaryngology at Helsinki University Hospital in 2013 were retrospectively enrolled. The data were collected from patients' hospital medical records, the laboratory database and radiological reports. Results: Odontogenic origin of ARS was suspected in 59 (15.3%) patients. Altogether (29.9%) 115 patients complained of unilateral symptoms and these were found to associate with probable oral microbial findings (p < .001). These findings covered 20.2% of isolates. Teeth were mentioned in 89.6% of the radiological reports. Conclusions and significance: OS is common among patients with ARS, and good diagnostic tools already exist in routine practice. Microbial and radiological findings should be carefully evaluated, especially in cases of unilateral symptoms.

Smoking or poor oral hygiene do not predispose to peritonsillar abscesses via changes in oral flora.

Aim: The purpose of this prospective study was to determine if there is a difference in number and distribution of salivary bacteria between patients with tonsillar infection and healthy volunteers. Background: The etiology of peritonsillar abscess (PTA) is unclear. Smoking, periodontal disease, and infection of minor salivary glands have been suggested as predisposing factors for PTA. Material and methods: Patients with acute tonsillitis (AT) (n = 54), peritonsillitis (PT) (n = 36), PTA (n = 58), and healthy volunteers (n = 52) were prospectively recruited and evaluated. Saliva bacteria were analyzed with flow cytometry. Patients and their treating physicians completed a questionnaire about patients' current disease, smoking habits, alcohol consumption, and oral health. Results: There were no differences in the total number of saliva bacteria between patients with acute throat infection and healthy volunteers (p = .104) or between AT, PT, and PTA patients (p = .273). Smoking habits, alcohol consumption, oral hygiene, or prior antibiotics had no effect on total amount of salivary bacteria in patients with acute throat infection. Conclusions: The effects of smoking on salivary bacteria do not seem to be the mechanism that promotes development of PTA in smokers.

Diagnostics of rare disorders: whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders.

BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKC), the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs. METHODS: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions. RESULTS: In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients. CONCLUSIONS: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.

Interactions between the Aggregatibacter actinomycetemcomitans secretin HofQ and host cytokines indicate a link between natural competence and interleukin-8 uptake.

Naturally competent bacteria acquire DNA from their surroundings to survive in nutrient-poor environments and incorporate DNA into their genomes as new genes for improved survival. The secretin HofQ from the oral pathogen Aggregatibacter actinomycetemcomitans has been associated with DNA uptake. Cytokine sequestering is a potential virulence mechanism in various bacteria and may modulate both host defense and bacterial physiology. The objective of this study was to elucidate a possible connection between natural competence and cytokine uptake in A. actinomycetemcomitans. The extramembranous domain of HofQ (emHofQ) was shown to interact with various cytokines, of which IL-8 exhibited the strongest interaction. The dissociation constant between emHofQ and IL-8 was 43 nM in static settings and 2.4 µM in dynamic settings. The moderate binding affinity is consistent with the hypothesis that emHofQ recognizes cytokines before transporting them into the cells. The interaction site was identified via crosslinking and mutational analysis. By structural comparison, relateda type I KH domain with a similar interaction site was detected in the Neisseria meningitidis secretin PilQ, which has been shown to participate in IL-8 uptake. Deletion of hofQ from the A. actinomycetemcomitans genome decreased the overall biofilm formation of this organism, abolished the response to cytokines, i.e., decreased eDNA levels in the presence of cytokines, and increased the susceptibility of the biofilm to tested ß-lactams. Moreover, we showed that recombinant IL-8 interacted with DNA. These results can be used in further studies on the specific role of cytokine uptake in bacterial virulence without interfering with natural-competence-related DNA uptake.

Identification of a novel bacterial outer membrane interleukin-1Β-binding protein from Aggregatibacter actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans is a gram-negative opportunistic oral pathogen. It is frequently associated with subgingival biofilms of both chronic and aggressive periodontitis, and the diseased sites of the periodontium exhibit increased levels of the proinflammatory mediator interleukin (IL)-1ß. Some bacterial species can alter their physiological properties as a result of sensing IL-1ß. We have recently shown that this cytokine localizes to the cytoplasm of A. actinomycetemcomitans in co-cultures with organotypic gingival mucosa. However, current knowledge about the mechanism underlying bacterial IL-1ß sensing is still limited. In this study, we characterized the interaction of A. actinomycetemcomitans total membrane protein with IL-1ß through electrophoretic mobility shift assays. The interacting protein, which we have designated bacterial interleukin receptor I (BilRI), was identified through mass spectrometry and was found to be Pasteurellaceae specific. Based on the results obtained using protein function prediction tools, this protein localizes to the outer membrane and contains a typical lipoprotein signal sequence. All six tested biofilm cultures of clinical A. actinomycetemcomitans strains expressed the protein according to phage display-derived antibody detection. Moreover, proteinase K treatment of whole A. actinomycetemcomitans cells eliminated BilRI forms that were outer membrane specific, as determined through immunoblotting. The protein was overexpressed in Escherichia coli in both the outer membrane-associated form and a soluble cytoplasmic form. When assessed using flow cytometry, the BilRI-overexpressing E. coli cells were observed to bind 2.5 times more biotinylated-IL-1ß than the control cells, as detected with avidin-FITC. Overexpression of BilRI did not cause binding of a biotinylated negative control protein. In a microplate assay, soluble BilRI bound to IL-1ß, but this binding was not specific, as a control protein for IL-1ß also interacted with BilRI. Our findings suggest that A. actinomycetemcomitans expresses an IL-1ß-binding surface-exposed lipoprotein that may be part of the bacterial IL-1ß-sensing system.

[Herpes simplex]. / Herpes simplex--virusinfektioiden nykykuva ja hoito.

Current picture and treatment of herpes simplex virus infections The contraction of primary herpes simplex infection in early childhood is becoming increasingly less frequent. A growing number of new cases of genital herpes are caused by HSV-1. Excretion of virus by carriers of genital herpes often takes place also during the asymptomatic stage and symptomless recurrences of genital herpes may be very brief in duration. Primary infections and reactivations can be treated with anti-herpes medication. Progress in drug treatment has taken place in the treatment of serious infections of the newborn and in the preventive treatment of herpes reactivations, in which fairly large single doses have proven effective.

Vasodilator isoxsuprine alleviates symptoms of oral submucous fibrosis.

OBJECTIVES: The aim of the study was to compare the effectiveness of vasodilator isoxsuprine to dexamethasone with hyaluronidase injections and physiotherapy in the treatment of oral submucous fibrosis. MATERIALS AND METHODS: Forty patients with oral submucous fibrosis were randomly assigned into three groups. Group A patients (n = 15) received 10 mg isoxsuprine tablets four times per day, group B (n = 15) biweekly dexamethasone with hyaluronidase intralesional injections, and group C (n = 10) placebo tablets. In addition, all patients were instructed physiotherapy exercises. The treatment time was 6 weeks and patients were followed-up for 4 months thereafter. The effect of the treatment was evaluated by measurements of inter-incisal distance and oral burning sensation and evaluation of histological findings of the diseased mucosa. RESULTS: Mouth opening increased and burning sensation decreased significantly in all groups, but the effects were significantly greater in groups receiving either oral isoxsuprine or dexamethasone with hyaluronidase injections in addition to physiotherapy. The decrease in burning sensation occurred more rapidly in patients receiving intralesional dexamethasone with hyaluronidase. Histological improvement was not observed in any of the groups. CONCLUSIONS: Oral isoxsuprine as well as dexamethasone with hyaluronidase injections combined to physiotherapy alleviate symptoms of oral submucous fibrosis significantly more efficiently than physiotherapy alone. CLINICAL RELEVANCE: Oral isoxsuprine can be considered as a new candidate drug for the treatment of oral submucous fibrosis. Physiotherapy exercises provide relief of symptoms and should be instructed to all patients.

Rate of evolution and molecular epidemiology of tick-borne encephalitis virus in Europe, including two isolations from the same focus 44 years apart.

Tick-borne encephalitis virus (TBEV) is a member of the family Flaviviridae. It is transmitted by Ixodes spp. ticks in a cycle involving rodents and small mammals. TBEV has three subtypes: European, Siberian and Far Eastern. The virus causes thousands of cases of meningoencephalitis in Europe annually, with an increasing trend. The increase may be attributed to a complex network of elements, including climatic, environmental and socio-economic factors. In an attempt to understand the evolutionary history and dispersal of TBEV, to existing genetic data we add two novel complete ORF sequences of TBEV strains from northern Europe and the completion of the genome of four others. Moreover, we provide a unique measure for the natural rate of evolution of TBEV by studying two isolations from the same forest on an island in Åland archipelago 44 years apart. For all isolates, we analysed the phylogeny, rate of evolution and probable time of radiation of the different TBEV strains. The results show that the two lineages of TBEV in different Ixodes species have evolved independently for approximately 3300 years. Notably, rapid radiation of TBEV-Eur occurred approximately 300 years ago, without the large-scale geographical clustering observed previously for the Siberian subtype. The measurements from the natural rate of evolution correlated with the estimates done by phylogenetic programs, demonstrating their robustness.

Human lactoferrin but not lysozyme neutralizes HSV-1 and inhibits HSV-1 replication and cell-to-cell spread.

The frequent oral shedding of herpes simplex virus type 1 (HSV-1) in the absence of clinical disease suggests that symptomatic HSV-1 recurrences may be inhibited by the mucosal environment. Indeed, saliva has been shown to contain substances with anti-HSV activity. In the current study, we investigated the anti-HSV-1 activity of human lactoferrin (hLf) and lysozyme (hLz), two highly cationic polypeptides of the mucosal innate defence system. HLf blocked HSV-1 infection at multiple steps of the viral replication cycle, whereas lysozyme displayed no anti-HSV-1 activity. Preincubation of HSV-1 virions and presence of hLf during or after viral absorption period or for the entire HSV-1 infection cycle inhibited HSV-1 infection by reducing both the plaque count and plaque size in a dose- and virus strain-dependent manner. Cell-to-cell spread of wild-type HSV-1 and the strain gC-39, deleted of glycoprotein C, was dramatically reduced, but the cell-to-cell spread of HSV-1 Rid1, harboring a mutated gD and thus unable to react with the cellular HVEM receptor, remained unchanged. This suggests that the inhibition of cell-to-cell spread is mediated by effects on gD or its cellular counterparts. Our results show that the cationic nature is not a major determinant in the anti-HSV action of mucosal innate cationic polypeptides, since whereas hLf inhibited HSV-1 infection efficiently, hLz had no HSV-1 inhibiting activity. Our results show that in addition to inhibiting the adsorption and post-attachment events of HSV-1 infection, hLf is also able to neutralize HSV-1 and that the inhibition of cell-to-cell spread involves viral gD. These results suggest that Lf may have a significant role in the modulation of HSV-1 infection in the oral cavity as well as in the genital mucosa, the major sites of HSV-1 infection.

Subtly impaired humoral immunity predisposes to frequently recurring genital herpes simplex virus type 2 infection and herpetic neuralgia.

BACKGROUND: Immunogenetic factors predisposing to recurrent genital herpes remain poorly characterized. METHODS: In a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed. RESULTS: The G3m(g),G1m(a/a(x)) haplotype was more frequent in patients than in HSV-seronegative control subjects (P=.047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P=.001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P=.001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P=.022). CONCLUSIONS: Low levels of antibody-dependent cellular cytotoxicity-mediating IgG1 and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.