Human herpesvirus 7 viral encephalitis after allogeneic hematopoietic stem cell transplantation: report of three cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics, diagnosis, treatment and outcome of patients with human herpesvirus 7 (HHV-7) viral encephalitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical manifestations, laboratory characteristics, diagnosis and treatment process and outcome of 3 patients with HHV-7 viral encephalitis after allo-HSCT in Hebei Yanda Lu Daopei Hospital from 2018 to 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The clinical features of 3 patients with HHV-7 viral encephalitis after allo-HSCT included fever, headache, vomiting, apathy, etc., without specific symptoms or signs. The conventional white blood cell count in the cerebrospinal fluid was normal or slightly higher, mainly lymphocytes, and the cerebrospinal fluid protein was normal or slightly higher. The HHV-7 virus DNA in cerebrospinal fluid was positive, and the treatment with ganciclovir or foscarnet was effective. The prognosis was favorable in two mild cases, but one case with cerebral hemorrhage died eventually.Conclusions:HHV-7 viral encephalitis is a rare infection after allo-HSCT, and it can be easily misdiagnosed due to lack of typical symptoms and indications for routine laboratory tests. The detection of HHV-7 DNA in the cerebrospinal fluid can help confirm the diagnosis. Currently, there is no standard treatment programs, but ganciclovir and foscarnet are effective.

Analysis of Drug Therapy for a Case of Child with Human Herpesvirus 7 Infection in Central Nervous System by Clinical Pharmacist / 中国药房

OBJECTIVE：To investigate the r ole of clinical pharmacists on the therapy for human herpesvirus 7（HHV-7） infection in central nervous system. METHODS ：The clinical pharmacists participated in the treatment process of the hospitalized patient who was a 15-year-old patient with central nervous system infection. The doctor initially gave Levetiracetam tablets （500 mg，bid，po）to control epilepsy symptoms ，and Acyclovir for injection （500 mg，q8 h，ivgtt）for antiviral treatment. According to the large red wheal scattered rubella on the limbs and back of the patient ，clinical pharmacists recommended to give Dexamethasone sodium phosphate injection （10 mg，qd，iv）and Loratadine tablets （10 mg，qd，po）for anti-allergy treatment ；in view of involuntary shaking of limbs in the patient ，clinical pharmacists recommended to continue to give Dexamethasone sodium phosphate injection intravenously to control inflammation and Xingnaojing injection （20 mL，qd，ivgtt） to improve the convulsion. For HHV- 7 infection，based on consulting the relevant guidelines and existing treatment experience ，the clinical pharmacists recommended discontinuation of acyclovir ， dexamethasone combined with Human immunoglobulin （pH 0278）（17.5 g，qd，ivgtt）for impact therapy should be used and adverse drug reactions and therapeutic effects should be monitored at the same time. RESULTS ： The physiciansaccepted the suggestions of clinical pharmacists. The patient was improved and discharged from the hospital after 18 days of treatment. CONCLUSIONS ： During the treatment of ineffective case of clinic rare central nervous system infectious diseases with routine a ntiviral drugs ，clinical pharmacists assisted physicians to improve their treatment plan and ensure the effectiveness and safety of patient ’s medication.

Polirradiculoneuritis aguda asociada a infección por Virus Herpes Humano 7 en un paciente adulto inmunocompetente / Acute polyradiculoneuropathy associated with human Herpes Virus 7 in an immunocompetent patient: case report

Human herpes virus 7 (HHV-7) is a cause of encephalitis, meningitis and myeloradiculoneuropathy in adults who are immunocompetent or with immunosuppression. The involvement of the peripheral nervous system is always associated with myelitis. We report a case of acute polyradiculoneuropathy due to HHV-7, without involvement of central nervous system, in an immunocompetent patient. A 35-years-old man complained of lumbar pain radiating to both buttocks. On examination muscle strength and tendon reflexes were normal. He had asymmetric pinprick and light touch saddle hypoesthesia and also in the perineal region, dorsum and lateral aspect of the left foot. Magnetic resonance imaging showed mild thickening and contrast enhancement of cauda equina nerve roots. Polymerase chain reaction performed on cerebrospinal fluid was positive for HVV-7. Other inflammatory, infectious and neoplastic etiologies were ruled out. Lumbar pain and hypoesthesia improved progressively and neurological examination was normal after one month. He did not receive antiviral therapy.

Detection of human herpesvirus type 7 infection in patients with drug eruptions / 中华皮肤科杂志

Objective To investigate the role of human herpesvirus type 7 (HHV-7) in the development of drug eruptions.Methods Venous blood samples were collected from 35 patients with mild drug eruptions at acute stage,15 patients with severe drug eruptions at both acute stage and remission stage,as well as 50 healthy human controls.PCR was performed to detect HHV-7 DNA in peripheral blood mononuclear cells (PBMCs),and enzymelinked immunosorbent assay (ELISA) to determine the titer of anti-HHV-7 IgM antibody in serum.Statistical analysis was carried out by t test,one way analysis of variance,Chi-square test and q test.Results The detection rate of HHV-7 DNA was significantly higher in these patients with drug eruptions than in the healthy controls (82.00％ (41/50) vs.62.00％ (31/50),x2 =4.96,P ＜ 0.05),different among patients with severe drug eruptions (93.33％ (14/15)),patients with mild drug eruptions (77.14％ (27/35)) and the healthy controls (x2 =6.32,P ＜ 0.05),higher in the patients with severe drug eruptions than in the healthy controls (q =3.50,P ＜ 0.05),but not significantly different between the patients with severe drug eruptions at acute stage and those at remission stage (73.33％(11/15),P ＞ 0.05).The anti-HHV-7 IgM antibody titer was significantly increased in the patients with drug eruptions compared with the healthy controls ((69.319 0 ± 25.289 7) ng/L vs.(59.785 3 ± 22.438 2) ng/L,t =1.99,P ＜ 0.05),but no significant difference was observed among the patients with severe drug eruptions (74.340 7 ±31.411 2) ng/L),patients with mild drug eruptions ((65.479 1 ± 21.326 1) ng/L) and healthy controls (P ＞ 0.05) or between HHV-7 DNA-positive patients ((63.748 1 ± 27.239 1) ng/L) and-negative patients ((65.580 2 ± 36.258 4) ng/L,P ＞ 0.05).Conclusions Active HHV-7 infection exists in patients with drug eruptions,and may be associated with the development and aggravation of this entity.

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment / Linfocitopenia T CD4+ grave, en individuos negativos para virus de immunodeficiencia humana, mejoró con tratamiento antivirus herpes humanos

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings' health.

Múltiples enfermedades bacterianas, micóticas, parasitarias y virales pueden asociarse con linfocitopenia y linfocitopenia CD4+. También enfermedades autoinmunes, neoplásicas, inmunodeficiencia común variable, estrés físico, sicológico o traumático, la malnutrición y el tratamiento con inmunosupresores. Esta condición también se presenta sin causa aparente y es conocida como linfocitopenia T CD4+ idiopática. Entre las infecciones virales, los retrovirus, especialmente el virus de inmunodeficiencia humana, es la más frecuente causa, pero muchas otras infecciones virales agudas, entre ellas, la mononucleosis por citomegalovirus y por Epstein Barr virus, se asocian con linfocitopenia total y linfocitopenia T CD4+, que son transitorias y se recuperan cuando la enfermedad mejora. Una linfocitopenia grave asociada con infección crónica por virus herpes humanos y que mejore con el tratamiento de ellos, no ha sido publicada. Se describen 6 pacientes, negativos para virus de inmunodeficiencia humana, con linfocitopenia total y linfocitopenia T CD4+ graves y con manifestaciones clínicas de inmunodeficiencia celular, quienes respondieron rápidamente al tratamiento con ganciclovir o valganciclovir. Es importante considerar la infección crónica por virus herpes humanos en el diagnóstico diferencial de la etiología de la linfocitopenia T CD4+ en individuos no infectados por el virus de inmunodeficiencia humana, para iniciar un tratamiento efectivo de los pacientes y determinar en futuros estudios el impacto de la infección crónica por herpes virus en la salud humana.

Meningomielitis asociadas a infección por herpes virus humano 7: Comunicación de dos casos / Meningomyelitis associated with infection by human herpes virus 7: Report of two cases

Human herpesvirus 7 (HHV-7) may cause encephalomyelitis in immune competent adults. We report two patients infected by the virus. A 34-year-old male presenting with paraparesis and a sensitive deficiency located in D6 dermatome. Cerebrospinal fluid had 35 white blood cells per mm³ and 75 mg protein per dl. A PCR-microarray examination was positive for HHV-7. The patient was treated with prednisolone and ganciclovir with full recovery. A 27-year-old male presenting with headache, fever and diarrhea. Cerebrospinal fluid analysis showed 160 cells per mm³ and 75 mg protein per dl. Viral RNA detection was positive for HHV-7. The patient was managed with analgesia and rest and was discharged with the diagnosis of viral meningitis. Our communication supports the notion that HHV-7 may be considered as pathogen factor in humans, even in immune competent ones.

An analysis of etiological and genetic factors of a patient with familial hemophagocytic lymphohistiocytosis / 中华内科杂志

Objective To analyze the etiological factor and genetic feature of a familial hemophagocytic lymphohistiocytosis patient with PRF1 mutation (FHL2) with human herpesvirus 7 (HHV7)infection and its family constellation. Methods Clinical characteristics, laboratory examinations of a FHL2 case with HHV7 infection were reported. HHV1-HHV8 virus DNA was screened by PCR; NK cell function was analyzed by flow cytometry; PRF1 gene mutations were analyzed by PCR and direct sequencing, structure of mutant PRF1 proteins were analyzed using ExPasy and I-TASSER server and genetics pedigree were analyzed. Results The patient's HHV7 viral was detected positive with DNA copy number of 350/106 peripheral nucleated cells. Flow cytometry analysis showed decrease both in proportion of perforin positive NK cells and perforin protein expression. Genetic testing showed PRF1 biallelic heterozygote mutations (c. 503G ＞ A/p. S168N and c. 1177T ＞ C/p. C393R) and pedigree analysis showed they were inherited. The patient was then treated with antivirus therapy, dexamethasone and VP16 therapy, but only achieved partial response. The patient was then followed by human leukocyte antigen 10/10 allele identical nonconsanguinity allogeneic hematopoietic stem cell transplantations (allo-HSCT) and soon the successful implantation of donor hematopoietic cells and persistent recovery was achieved. The patient was now surviving without recurrence for 9 months after allo-HSCT. Conclusions FHL is prone to be misdiagnosed as lymphoma. Genetic analysis of related gene mutation and herpes simplex virus detection will help in early and accurate diagnosis. Allo-HSCT is a fundamental treatment of FHL.

Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients / Detecção de herpesvirus humano-7 por nested-PCR qualitativo: comparação entre indivíduos sadios e receptores de transplante hepático

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3 percent of leukocytes and 0 percent of serum. human herpesvirus-7 was detected in sera of 48.2 percent of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.

Diagnóstico da infecção ativa pelo herpesvirus humano-7 é difícil devido ao fato deste vírus ser ubíquo e poder causar infecção persistente no hospedeiro. O significado da detecção do DNA viral por reação em cadeia da polimerase não é claro e, reações cruzadas podem ocorrer em testes sorológicos. O objetivo deste estudo foi avaliar a nested-PCR para detectar infecção ativa pelo herpesvirus-7 em receptores hepáticos comparando com indivíduos sadios. Nested-PCR para herpesvirus-7 foi realizado em leucócitos e soro de 53 voluntários sadios e em soro de 29 receptores hepáticos. Nos voluntários sadios, herpesvirus-7 foi detectado em 28,3 por cento de leucócitos e 0 por cento de soro. herpesvirus-7 foi detectado em soro de 48,2 por cento de receptores hepáticos. Nested-PCR em DNA extraído de leucócitos detectou infecção latente e o estudo sugere que nested-PCR realizada em soro poderia ser útil para detectar infecção ativa por herpesvirus-7 em receptores de fígado.

Human Herpesvirus 7 Glycoprotein B (gB) , gH, gL, gO Can Mediate Cell Fusion / 生物化学与生物物理进展

Human herpesvirus 7 (HHV-7) infection is dependent on the functions of structural glycoproteins at multiple stages of the viral life cycle. These proteins mediate the initial attachment and fusion events that occur between the viral envelope and a host cell membrane, as well as cell to cell spread of the virus. To characterize the HHV-7 glycoproteins that can mediate cell fusion, a cell-based fusion assay was used. 293T cells expressing the HHV-7 glycoproteins of interest along with a luciferase reporter gene under the control of the T7 promoter were cocultivated with SupT1 cells transfected with T7 RNA polymerase. HHV-7 glycoproteins gB, gH, gL and gO can mediate the fusion of 293T cells with SupT1 cells, and the fusion can be inhibited by anti-CD4 mAbs. Thus, the coexpression of HHV-7 gB, gO, gH and gL is sufficient and necessary for HHV-7 induced membrane fusion, and one of these glycoproteins or protein complex formed by these glycoproteins might be the ligand(s) of CD4 molecule.