Herpes simplex virus type I-infected disorders alter the balance between Treg and Th17 cells in recurrent herpes labialis patients.

Recurrent herpes labialis (RHL) is a common skin disease that is often caused by herpes simplex virus type I (HSV-1), but its immunology and pathogenesis remain unclear. The balance of Th17/Treg cells is crucial for maintaining immune homeostasis. This study aimed to investigate whether the balance of Th17/Treg cells and related cytokines may be a determinant occurrence in patients with RHL. This is a clinical experimental research based on clinical observation and analysis. We collected RHL patients from the outpatient clinic of the Department of Dermatology of Zhejiang Chinese Medical University (Hangzhou, China) in 2017, conducted questionnaire survey and signed informed consent. Peripheral blood was collected from 30 patients with RHL and 30 healthy volunteers. Flow cytometry was used to detect the percentages of Treg cells and Th17 cells. Protein microarrays coated with 20 cytokines related to T-cell subsets were performed. Enzyme-linked immunosorbent assay (ELISA) assay was conducted to further verify the expression levels of the cytokines that were screened by protein microarrays. Percentages of Th17/Treg cells in peripheral blood of RHL patients were significantly increased compared to those in healthy volunteers. The fold changes of GM-CSF, IL-4, TGF-ß, IL-12, IL-10, IL-17F, and TNF-α were significantly increased compared with healthy volunteers. In addition, the expression of IL-4, IL-10, and TGF-ß in the serum of RHL patients increased significantly. Our results indicated an imbalance of Th17/Treg cells in RHL, and this imbalance is probably an important factor in the occurrence, development, and recovery of RHL.

Vitamin D Levels in Patients with Recurrent Herpes Labialis.

Recurrent infections of herpes simplex virus in the orolabial area are known as recurrent herpes labialis (RHL). Vitamin D has been shown to have an important immunomodulatory role and to be associated with several infectious diseases. This hospital-based case-control study aimed at investigating the association between vitamin D and RHL by comparing vitamin D levels in individuals with and without RHL. Individuals who presented to the dermatology clinic at a state hospital due to RHL (n = 50) and matching control group of healthy volunteers (n = 51) were studied. Their vitamin D levels were measured, stratified based on clinical guidelines, and compared. The average serum vitamin D (25-hydroxyvitamin D) levels were 23.8 ± 15.5 and 42.0 ± 26.3 nM in the patient and control groups, with significant differences between their average serum vitamin D levels and vitamin D status. The studied population had serious vitamin D deficiency regardless of having RHL, with vitamin D levels below the adequate limits in more than 96% of the population. Most importantly, the study established a significant association between low serum vitamin D levels and the presence of RHL. Further interventional and pathophysiological studies should clarify the nature and mechanism of the relationship.

Ceruloplasmin plasma levels in patients with severe forms of herpes infection.

BACKGROUND: Research interest in ceruloplasmin (CP) has significantly increased in recent years owing to new discoveries of its properties including anti-inflammatory and anti-oxidant effects. Data on CP blood plasma level in patients with herpetic infection caused by herpes simplex virus are scarce and often contradictory. Most point to a reduction of CP in the blood plasma of patients during the exacerbation of the disease with gradually return to normal values after treatment. There is evidence of an increase in CP levels during the acute period of CRHI (chronic recurrent herpes infection) and decrease in remission. MATERIALS AND METHODS: The content of ceruloplasmin in blood plasma was determined by immunoturbidimetry using the test-systems "Spinreact" (Spain) and biochemical analyzer "Architect C8000". RESULTS: We found that in patients with severe forms of chronic recurrent herpes infection in the exacerbation period, CP levels were increased by approximately 35% relative to the control values. However in the remission period in 80% of patients, CP concentrations remained elevated and in some patients the CP level was even increased in comparison with values in the exacerbation. Such dynamics of CP were not caused by the exacerbation of concomitant diseases. CONCLUSION: The increased CP levels in the remission period in patients with severe forms of chronic recurrent herpes infection may have been caused by its effect as an endogenous antioxidant. No correlations of CP levels with other laboratory signs of acute inflammation were found but identified was a relation to free radical activity.

Detection of herpes simplex virus DNA in plasma of patients with primary but not with recurrent infection: implications for transfusion medicine?

Among the family of herpes viruses, only cytomegalovirus (CMV) and, to a lesser extent, human herpes virus 8 (HHV-8) are of relevance in transfusion medicine. Due to neutropism, herpes simplex viruses (HSV) types 1 and 2 are considered to be of minor relevance. However, several reports gave evidence that a HSV DNAemia might occur and HSV could therefore be transmissible by blood products. The aim of our study was to collect data about prevalence of HSV antibodies among blood donors and to clarify whether HSV DNAemia is possible. HSV antibody states of 653 blood donors were investigated. Blood specimens of 46 patients with primary and recurrent HSV infection were tested for HSV-1 and HSV-2 DNA using TaqMan polymerase chain reaction. In 505 of the 653 blood donors HSV antibodies were detectable, most of which were HSV-1 antibodies. HSV DNA was detected in plasma, but not in peripheral blood mononuclear cells (PBMCs) of seven rather seriously ill patients with primary herpes genitalis. No HSV viraemia was detectable in otherwise healthy patients with recurrent herpes labialis. Thus, HSV DNAemia is possible, but seems to be limited to primary infections and could not be detected in the recurrent infection. Therefore, blood donors with primary herpes infection should be deferred from donation. Blood donors with recurrent HSV infection are probably not at risk of transmitting HSV, but further studies are necessary to prove this hypothesis. Detection of HSV DNA in PBMCs as described formerly could not be confirmed by this study.

Widespread unilateral pain associated with herpes simplex virus infections.

UNLABELLED: We describe a patient group with unexplained widespread pain on one side of the body and pain exacerbations during active labial or genital herpes and during herpetic central nervous system infections. The patients had no visible lesion of the central nervous system on magnetic resonance imaging or abnormality in electrophysiological studies. To understand the nature of the pain and its possible relation to herpes simplex virus (HSV) infections, a clinical neurological examination was performed and quantitative sensory testing and skin biopsies were assessed in 17 patients. The levels of serum total immunoglobulins and IgG subclasses and the frequencies of the immune response genes at the IGH@, HLA-A, -B, -DRB1, C4A, and C4B loci were analyzed in the patients and in control subjects. The patients manifested a uniform clinical syndrome with unilateral pain that was best described as neuropathic and that was exacerbated by HSV reactivations. Low plasma IgG3 concentrations, the presence of either low plasma IgG1 or IgG3 or both, and high anti-HSV-2-IgG titers were more common in the patients than in the control subjects, which rendered the patients more vulnerable to HSV recurrences. PERSPECTIVE: We suggest that low immunoglobulin subclass levels and certain MHC alleles render the patients susceptible to recurring HSV infections. HSV reactivations and the accompanying inflammatory process cause dysfunction of the central nervous system that manifests as neuropathic pain. Studies using functional brain imaging are needed to clarify this syndrome.

A comparative study between viral isolation and indirect immunofluorescence in the diagnosis of herpes simplex virus.

Fifty patients with oral ulcers were studied clinically and investigated for the detections of Herpes Simplex Virus (HSV) through virus isolation from their lesions (vesicles and ulcers) and detection of the presence of antiviral antibodies (both, IgM and IgG) in their sera using the indirect immunofluorescene (IIF) technique. The results of this study proved that virus isolation is the most reliable method for diagnosis, though the use of antibody serological tests could be a useful adjunct to virus isolation in situations where a rapid laboratory diagnosis is needed. Oral Herpes Simplex virus infection can be viewed, in the main, as a trivial disorder causing patients minor physical discomfort. The prevalence of HSV may be high in innocent infections, as high as 1/3 of the population. However, HSV infection and its complications with troublesome recurrences may make the problem worse. The apparent increase in HSV infection over recent years may be partly due to increased publicity about the disease, the current antiviral treatment, the inclusion of both primary and recurrent cases in clinic follow up and the increased use of viral cultures for diagnosis. The aim of this work is to share in the study of the detection of HSV through virus isolation and detection of antiviral antibodies using IIF technique, as well as the evaluation of the diagnosis by the above mentioned methods.

Detection of herpes simplex virus DNA in serum and oral secretions during acute recurrent herpes labialis.

Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which the virus may be present in the blood during a localized infection in otherwise healthy patients is still unknown. Literature on patterns of HSV shedding into the oral cavity at the prodromal stage of the disease, during recurrences, and also during asymptomatic periods is still lacking. The present study aims at the detection of HSV DNA in the serum and oral secretions during acute herpes labialis using a highly sensitive technique, the polymerase chain reaction (PCR). The study included 10 patients with acute herpes labialis and five healthy controls. Using PCR, herpes simplex virus DNA was detected in the serum of seven patients (70%) and in the saliva of nine patients (90%). One of the control cases showed positive HSV DNA in the saliva (20%). There was good statistical agreement between the presence of HSV DNA in the serum and saliva. Frequency of attacks, patient's age, and gender had no statistically significant effect on the presence of the virus in serum or in saliva. It is concluded that HSV viremia during attacks of recurrent herpes simplex is more frequent than previously appreciated.

Immune, stress, and mood markers related to recurrent oral herpes outbreaks.

This was a prospective and longitudinal study designed to compare daily mood states and weekly changes in plasma levels of immune and neuroendocrine markers with recurrent herpes labialis lesion recurrences during a 3-month period among 9 subjects. Results from a paired t test showed that there was a significant decrease in plasma levels of natural killer cells and serum levels of epinephrine from the week before recurrent herpes labialis lesion occurrence (T1,9 = 2.70; p < 0.05) to the week of recrudescence (T1,9 = 2.41; p < 0.05). On the other hand, in the week before recrudescence the number of natural killer cells was 58 units higher than the overall group mean for natural killer cell level (227 units). In the week before outbreak, elevated natural killer cell numbers were associated with a mood of discontentment (r = 0.64; p = 0.05). Elevated levels of epinephrine averaged across the 12 weekly blood draws were significantly correlated with higher scores on affect intensity (r = 0.72; p < 0.05). This study provides new data on the pattern of changes in stress, mood states, and immune and neuroendocrine markers associated with the recurrence of perioral herpes lesions. Putative mechanisms linking neuroendocrine and immune function are discussed.

Transient regression in lymphocyte count in B-cell chronic lymphocytic leukemia after viral infection.

Transient regression in the lymphocyte count of a patient with B-cell chronic lymphocytic leukemia (B-CLL) after viral infection is reported. A similar event occurred under natural interferon-alpha (IFN-alpha) treatment. It was confirmed that the event was not caused by a direct cytotoxic effect of IFN-alpha by analyzing the DNA fragmentation to estimate apoptotic and necrotic cell death before and after the administration of IFN-alpha. The study also suggested that the event was not caused by a cytostatic effect of IFN-alpha.

Detection of herpes simplex virus DNA in the peripheral blood during acute recurrent herpes labialis.

BACKGROUND: Although herpes simplex virus (HSV) has been detected in the peripheral blood of immunocompromised patients and in neonates with disseminated disease, the extent to which this virus may be present in the blood during a localized infection in otherwise healthy adults is unknown. OBJECTIVE: The purpose of this study was to determine whether HSV may be detected in the peripheral blood during acute recurrent herpes labialis. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from otherwise healthy adults with recurrent herpes labialis, both during an acute episode and several weeks after the lesions had healed. The PBMCs were examined for the presence of HSV with the polymerase chain reaction (PCR) and viral culture. RESULTS: By PCR, HSV DNA was detected in 7 of 34 specimens from an acute episode but in none of 24 specimens in the convalescent stage (p less than 0.004). PBMCs from seven donors, who were seronegative for HSV, were also negative for HSV by PCR. Viral cultures of 22 PBMC specimens were negative (including four specimens that were positive by PCR). CONCLUSION: The presence of HSV DNA in the blood is a transient phenomenon limited to the period of active infection in a minority of patients with herpes labialis, although it may be important in the development of disseminated disease as well as in the pathogenesis of herpes-associated cutaneous processes such as erythema multiforme.

Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis.

The amino acid lysine is an agent that has been proposed for treating the clinical symptoms of recurrent herpes simplex labialis. This study examined the efficacy of long-term prophylactic lysine supplementation. Twenty-six volunteers with a history of frequently recurring herpetic lesions completed a 12-month double-blind crossovers study. The experimental group received daily oral supplements of 1,000 mg 1-lysine. Serum samples were analyzed at scheduled intervals. In most instances, members of the lysine group reported significantly fewer lesions than the control group. Similarly, those who were taken off lysine supplementation generally showed a significant increase in lesion frequency. Quantitative hematologic measurements revealed the most clinically useful relationship. Data from this sample population indicated that when a person's serum lysine concentration exceeded 165 nmol/ml there was a corresponding significant decrease in recurrence rate. Conversely, the frequency rate increased significantly as concentration levels fell below 165 nmol/ml. These results suggest that prophylactic lysine may be useful in managing selected cases of recurrent herpes simplex labialis if serum lysine levels can be maintained at adequate concentrations.

Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis.

Interferon-gamma (IFN-gamma) was spontaneously secreted by peripheral blood mononuclear cells cultured from patients soon after recurrent herpes labialis (RHL) or was induced from macrophage-T lymphocyte cultures in vitro with HSV antigen. Circulating Leu-3+/Leu-2- cells produced the spontaneous IFN almost exclusively. In the HSV antigen-stimulated culture system the same subset was the predominant producer of IFN-gamma. The IFN-gamma producing leu-3+ lymphocytes were plastic nonaderent but nylon wool adherent, and may be analagous to the murine Th 2 helper cell. In contrast to one lymphocyte subset being the major IFN-gamma producer in this viral disease, mitogen stimulation induced IFN-gamma from all (Leu-2+/2- and Leu-3+/3-) subsets, with panning as the separation technique. As mitogens circumvent the normal processing and presentation of antigen, the RHL system described above may provide a more accurate picture of the relative contributions of helper (Leu-3+) and cytotoxic/suppressor (Leu-2+) T cells to IFN-gamma production in herpes viral disease.