HHV-6B- and HHV-7-associated choroiditis secondary to acute myelogenous leukemia: a case report.

We report a case of human herpes virus 6 (HHV-6)- and human herpes virus 7 (HHV-7)-associated choroiditis in an immunocompromised woman. A 42-year-old Chinese woman with a history of acute myelogenous leukemia presented with blurred vision and black floaters in her right eye. Anterior segment examination findings were normal. Ophthalmoscopic examination revealed a subretinal lesion in the superonasal peripapillary region with several punctate hemorrhages. Optical coherence tomography showed a crater-like choroidal protuberance, associated with retinal pigment epithelium rupture and full-thickness retinal edema in the involved area. Indocyanine green angiography demonstrated a broad hypofluorescent lesion in the choroid. The patient was diagnosed with choroiditis. Subsequently, metagenomic next-generation sequencing revealed HHV-6B and HHV-7 DNA in the aqueous humor. Therefore, antiviral therapy was initiated. The patient experienced resolution of all symptoms and signs after treatment with intravenous foscarnet and oral acyclovir. The findings in this case indicate that HHV-6 and HHV-7 can cause ocular infection, particularly in immunocompromised patients.

Characteristics of HHV-7 meningitis: a systematic review.

There are limited data on HHV-7 meningitis and this systematic review used electronic search to gather pieces of evidence regarding its characteristics. Nine articles were included which three were case reports and the rest of the articles were retrospective studies. Altogether, 32 cases were described in the literature that 13 were females and 26 were aged less than 16 years old. The HHV-7 meningitis has been reported in any season, especially in winter. It affected both immunocompetent and immunocompromised individuals and mostly presented with fever and headache, however rash and seizure have also been documented. The CSF analysis in general showed an elevated range of cell count with lymphocytic predominance and normal to slightly elevated protein levels. Thirteen patients did not receive treatment for HHV-7 meningitis and full recovery was gained in the majority of cases after about 10 days. This review summarizes characteristics of HHV-7 meningitis in the literature, and yet epidemiological studies are needed to shed more light which eventually could be helpful for the diagnosis and management of this disease.

Anti-N-methyl-D-aspartate receptor encephalitis and positive human herpesvirus-7 deoxyribonucleic acid in cerebrospinal fluid: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is a neuroautoimmune syndrome typically presenting with seizures, psychiatric symptoms, and autonomic dysfunction. Human herpesvirus-7 is often found with human herpesvirus-6 and infects leukocytes such as T-cells, monocytes-macrophages, epithelial cells, and central nervous system cells. The pathogenicity of human herpesvirus-7 is unclear. Cases of anti-N-methyl-D-aspartate receptor encephalitis with human herpesvirus-7 present in cerebrospinal fluid have been documented, but the clinical significance of this finding remains unclear. CASE PRESENTATION: An 11-year-old Caucasian boy was admitted to hospital after a generalized tonic-clonic seizure. Generalized tonic seizures repeated three more times during the day of hospitalization. Blood tests showed minor ongoing inflammation, while brain computed tomography yielded normal results. Brain magnetic resonance imaging showed hyperintense focal alterations in both temporal lobes, hippocampi, and at the base of the right frontal lobe. Positive anti-N-methyl-D-aspartate receptor antibodies were found in both serum and cerebrospinal fluid. Positive novel coronavirus 2 (severe acute respiratory syndrome coronavirus 2) immunoglobulin G antibodies were found in serum. Polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 was negative. Furthermore, positive human herpesvirus-7 deoxyribonucleic acid was found in cerebrospinal fluid. The patient was treated with acyclovir, human immunoglobulin, and methylprednisolone. The seizures did not repeat, and no psychiatric symptoms were present. The patient made a full recovery. CONCLUSIONS: We present a pediatric case of anti-N-methyl-D-aspartate receptor encephalitis with atypical clinical presentation. The role of human herpesvirus-7 in neurological disorders remains unclear in immunocompetent patients.

Prevalence of Anti-Human Herpes Virus Type 7 IgG Positivity Rate among Children with Fever and Skin Rash in Diyala Province, Iraq.

Human herpesvirus 7 (HHV-7) is a T-lymphotropic virus isolated from peripheral blood mononuclear cells as beta herpes viruses. It is a highly prevalent virus since over 90% of adults are seropositive. The majority of primary infection occurs in early childhood, and its prevalence peaks at 60 % in 11-13-year-old. This study was designed to investigate the seroprevalence of HHV- 7 infections among apparently healthy children as well as child patients with fever and skin rash in the Diyala community and its association with certain socio-demographic variables. The current study is a cross-sectional study conducted in Diyala province-Iraq, extending from July 2020 to March 2021. A total of 180 child patients with fever and skin rash were included. Their age range was 1-14years. Additionally, 60 healthy age-matched children were enrolled as a control group. A special questionnaire was prepared for this study, including socio-demographic information, clinical notes and the results of a complete blood count. Human privacy was esteemed by obtaining parents' verbal approval. Blood specimen was aspirated from all study groups. Sera were separated and kept at -20 °C until tested. Enzyme-linked immunosorbent assay (ELISA) kits for the detection of anti-HHV-7 IgG were used (Mybiosource-China). Statistical analysis was done using Statistical Package of Social Science (SPSS) version 27, and the P value was considered significant wherever it was less than 0.05. The anti-HHV-7 IgG positivity rate in patients was 19.4%, and that in healthy individuals was 31.7%, with an insignificant difference (P=0.051). The highest HHV-7 IgG positivity rate was found among patients 1-4 years old, matching that in the healthy group with a statistically insignificant difference (P=0.675). The gender, residence and number of children/ family insignificantly affect the distribution of HHV-7 IgG in the control group. The mean±SD of hemoglobulin (Hb) concentration among participants with negative anti-HHV-7 IgG was insignificant compared to their positive counterparts (P=0.987). The mean±SD of total WBC count among those positive for anti-HHV-7 IgG was insignificantly higher than their negative counterpart (P=0.945). The mean±SD lymphocyte count in patients and healthy control positive for anti-HHV-7 IgG were insignificantly higher (P=0.241) and (P=0.344), respectively. Lastly, healthy control positive for anti-HHV-7 IgG had insignificantly higher lymphocyte count (P=0.710). About one-third of healthy children in our community were seropositive for anti-HHV 7 IgG antibodies that are most prevalent at 1-4 years old and are insignificantly associated with gender, residence, and the number of children per family. Furthermore, the HHV-7 infection is insignificantly associated with alterations of complete blood count parameters.

Incidence and clinical features of HHV-7 detection in lower respiratory tract in patients with severe pneumonia: a multicenter, retrospective study.

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

Meningitis associated with HHV-7 in an Iranian immunocompetent adolescent girl.

There is limited literature regarding meningitis associated with HHV-7. This article reports an immunocompetent adolescent girl who developed fever, headache, and meningism which CSF molecular analysis with PCR was positive only for HHV-7. Interestingly, persistent cavum septum pellucidum and cavum vergae were observed on brain magnetic resonance imaging. The patient received antibiotics, dexamethasone, and acyclovir and then she gained full recovery. HHV-7 is a rare and yet possible pathogen in patients with meningitis, and this is the first described case report from Iran.

[Severe Encephalitis with Human Herpes Virus-7 (HHV-7) Associated Transient Splenial Lesion in an Immunocompetent Child: A Case Report]. / Immün Sistemi Saglam Çocukta Insan Herpes Virüs-7 (HHV-7) Iliskili Geçici Splenial Lezyon ile Birlikte Agir Ensefalit: Olgu Sunumu.

Encephalitis is the inflammation of the brain parenchyma accompanied by mental or behavioral neurological dysfunction, sensory or motor deficits, speech or movement disorders, and seizure. Encephalitis is an acute, life-threatening emergency that requires prompt recognition and a systematic approach for appropriate management. Human herpes virus (HHV-7) is one of the causative agents of encephalitis. In this report, a three years and six months old girl admitted to the hospital with the complaints of fever, cough, gushing vomiting, and altered consciousness, with fever, neck stiffness and blurred consciousness in her physical examination, and positive HHV-7 DNA polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) was presented. The CSF biochemistry of the patient was normal, and lymphocytic pleocytosis was detected in the CSF. Electroencephalography of the case revealed a cerebral dysfunction and hyperexcitability due to background activity abnormalities, and a cytotoxic transient lesion of the splenium in cranial magnetic resonance imaging. A 14-day foscarnet treatment was given to the patient after she progressed under empirical acyclovir treatment and HHV-7 was found to be the causative agent in the CSF. The patient was cured with the treatment and was followed up on an outpatient basis without any sequelae. In general, HHV-7 is estimated to be a common cause of pediatric acute encephalitis cases. It has been observed in the literature that almost all of the HHV-7-associated encephalitis cases occur after the age of six years, suggesting that HHV-7 causes neurological disease in children as a late infection. This case was three years and six months old and it was thought that she had encephalitis during primary infection. With this case report, we contributed to the literature by presenting a case of encephalitis in an immunocompetent pediatric patient with a transient splenial lesion associated with HHV-7, which progressed with empirical acyclovir treatment and responded to foscarnet treatment.

Frequency evaluation and molecular characterization of HHV-6 and HHV-7 among children under 5 years with fever and skin rash.

Skin rash is one of the most common complications during childhood. Viral agents play an essential role in the development of such symptoms. Present study aims to determine the prevalence and genetic variability of Human Herpesvirus 6 and 7 (HHV-6 and HHV-7) infections and their subtypes in children under 5 years of age with skin rash and negative for rubella and measles. We used serum and throat swap samples from 196 children with skin rash and fever. ELISA and IFA tests were performed to detect antibodies against HHV6/7. Sequencing was performed using Sanger sequencing, and BioEdit and MEGA10 software were used for sequence analysis. According to the results, 66% and 40% of cases were positive for HHV-6 IgM and HHV-7 IgM, respectively. According to the molecular analysis, HHV-6 Nested-PCR was positive in 18% of cases, however, HHV-7 Nested-PCR was positive in 7.7% of cases. On the other hand, HHV-6 IgG and HHV-7 IgG were positive in 91% and 55% of study cases, respectively. For HHV-6, we found some genetic variabilities resulting in antigenic changes compared to reference strains. HHV-7 isolates showed no genetic differentiation and had a stable gene sequence. Based on the results, the detection of some cases of HHV6/7 primary infection and the presence of specific symptoms of roseola in the study population needs continuous evaluation of HHV6/7 frequency and distribution, also genetic variabilities of HHV6. This can pave the way for investigating HHV6 immune evasion and vaccine research and studying the relationship between viral genetic variations and other factors like disease severity. Furthermore, it is necessary to determine the relation between HHV6 genetic changes and latent infection to be considered in possible future vaccines and antiviral drug development.

Anterior Uveitis Associated with Human Herpesvirus 7 Infection Diagnosed by Multiplex Polymerase Chain Reaction Assay: A Case Report.

BACKGROUND: Herpetic anterior uveitis (AU) is usually caused by the herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Herein, we report a case of herpetic AU associated with human herpesvirus 7 (HHV-7) infection. STUDY DESIGN: A case report. CASE PRESENTATION: A 49-year-old female patient presented with complaints of blurred vision and hyperemia in the right eye. Slit-lamp examination revealed bilateral fine and a few small white keratic precipitates (KPs), Descemet membrane folds in the right eye, and severe and mild cellular infiltration in the anterior chamber of the right and left eye, respectively. HHV-7 viral DNA was detected by a polymerase chain reaction assay of an aqueous humor sample. The AU improved significantly with topical steroids. CONCLUSION: We report a rare case of herpetic AU characterized by fine and small white KPs in which only HHV-7 DNA was detected in the aqueous humor.

Comprehensive analysis of HHV-6 and HHV-7-related gene signature in prognosis and response to temozolomide of glioma.

Human herpesvirus (HHV)-6 and HHV-7 have been detected in central nervous system and glioma tissue, while their exact role in glioma remains uncertain. Omics profiles and clinical information were downloaded from public databases, including The Cancer Genome Atlas cohort for training set and the Chinese Glioma Genome Atlas cohorts for validation sets. Differentially expressed genes between HHV-6 and HHV-7 infected or noninfected glioma patients were screened for establishing the HHV-6 and HHV-7 infection (HI) model through Lasso regression analysis. Bioinformatics methods were used to analyze the correlation between HI scores and prognosis, metastasis in glioma patients. Predictable efficacy of HI in temozolomide-resistance and HI-related genetic signatures were also explored. The HI model was constructed as: Risk score = (0.014709*DIRAS3) + (0.029787*TEX26) + (0.223492*FBXO39) + (0.074951*MYBL1) + (0.060202*HILS1). The five gene signature showed good performance in predicting survival time for glioma patients, while higher HI score is correlated with malignant features. Moreover, DNA mismatch repair genes were augmented in glioma patients with higher HI score as well as nonresponse to temozolomide treatment, which was in parallel with the transcriptomic result of temozolomide-resistant glioma cell. Targeting the five gene signature is beneficial for prognosis of glioma patients, especially in glioma patients underwent temozolomide treatment.

[Lymphadenitis possibly due to human herpesvirus 7 during methotrexate therapy for rheumatoid arthritis].

A 75-year-old woman who was treated with methotrexate (MTX) for rheumatoid arthritis was admitted to our hospital because of fever and loss of appetite. Physical examination revealed exanthems in the upper limbs and systemic lymphadenopathy. Her blood test showed elevated levels of serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R). Lymph node biopsy indicated atrophic follicles, interfollicular hyperplasia, and infiltration of macrophages phagocytosing nuclear debris and T-lymphocytes. This suggested lymphadenitis associated with viral infection. Human herpesvirus 7 (HHV-7) DNA was detected in the lymphoid tissue using polymerase chain reaction. The patient was successfully treated with MTX discontinuation and short-term administration of dexamethasone. Her symptoms improved, and LDH and sIL-2R levels were normalized. Human herpesvirus reactivates in patients with immunodeficiency on MTX administration. To the best of our knowledge, this is a valuable case of lymphadenitis considered to have been caused by HHV-7.

Development of a PCR assay for the detection of human herpes virus type 7.

A PCR assay has been developed to identify the DNA of the human herpes virus type 7. The search and selection of conserved regions was carried out by comparing the whole genome nucleotide sequences of HHV-7. A fragment duplicated in the HHV-7 genomes was chosen as a target for amplification. The performance of the assay was tested on a synthetic matrix and clinical samples. The developed assay has high sensitivity and specificity and showed good efficiency in detecting HHV-7 DNA in clinical samples.

Human herpesvirus 7 encephalitis in an immunocompetent adult and a literature review.

BACKGROUND: Human herpesvirus 7 (HHV-7) is a common virus that infects children early and is accompanied by lifelong latency in cells, which is easy to reactivate in immunodeficient adults, but the underlying pathological mechanism is uncertain in immunocompetent adults without peculiar past medical history. Even though the clinical manifestation of the encephalitis caused by HHV-7 is uncommon in immunocompetent adults, the HHV-7 infection should not be neglected for encephalitis for unknown reasons. CASE PRESENTATION: We reported here a case of HHV-7 encephalitis with epileptic seizures. While the brain computer tomography was standard, electroencephalography displayed slow waves in the temporal and bilateral frontal areas, then HHV-7 DNA was detected in the metagenomic next-generation sequencing of cerebrospinal fluid. Fortunately, the patient recovered after treatment and was discharged 2 months later. We also collected the related cases and explored a better way to illuminate the underlying mechanism. CONCLUSION: The case indicates clinicians should memorize HHV-7 as an unusual etiology of encephalitis to make an early diagnosis and therapy.

Investigation of the association between the antibody responses to neurotropic viruses and dementia outcomes in the UK Biobank.

The causes that trigger the onset of dementia are still unknown. Recently there has been an increasing interest in the possible role of infectious agents in the brain in the pathogenesis of this condition. Amongst the viruses, members of the Herpesviridae family, namely herpes simplex virus-1 (HSV1), cytomegalovirus (CMV), human herpesvirus-6 (HHV6), human herpesvirus-7 (HHV7) and varicella zoster virus (VZV) have been suggested as potential causes of the disease. However, the relative importance of these and other viruses in contributing to dementia remains unclear. We evaluated the association between seropositivity status of all viruses available in a large, population-based dataset (the UK Biobank) and dementia risk in an unbiased way. Of the 15 viruses investigated, our results showed a statistically significant increase of dementia risk associated only with HSV1 seropositivity (OR 2.14, 95% C.I. 1.21-3.81). However, by combining the data we found that seropositivity for 4 viruses (HSV1, HHV6, HHV7 and VZV) also significantly increases the risk of dementia (OR = 2.37, 95% C.I. 1.43-3.92). These four viruses have been described previously as neurotropic viruses. Our results provide support for a role for neurotropic viruses in the pathology of dementia.

Herpesvirus and neurological manifestations in patients with severe coronavirus disease.

BACKGROUND: Certain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms. METHODS: We analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method. RESULTS: Among the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034). CONCLUSIONS: The findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.