Acute ascending necrotizing myelitis in Okinawa caused by herpes simplex virus type 2

Summary A case of rapidly progressing ascending myelitis was necropsied. Necrosis was present throughout the whole length of the spinal cord and involved both the grey and white matter randomly. The perivascular lymphocytic infiltration in the spinal cord in the present case was more pronounced than that in the previously reported two cases of necrotizing myelopathy associated with malignancy. Using immunoperoxidase staining the presence of herpes simplex virus type 2 (HSV 2) antigen was demonstrated. Electron microscopic examinations revealed large numbers of HSV particles in the spinal cord. HSV 2 may be a common aetiological agent of necrotizing myelopathy and myelitis in Okinawa, an HSV 2 endemic area. In the present case, the necrosis was mainly found in the spinal cord but was also observed, to a very limited extent, in the brain.     

Effects of Prophylactic Foscarnet on Human Herpesvirus-6 Reactivation and Encephalitis in Cord Blood Transplant Recipients: A Prospective Multicenter Trial with an Historical Control Group

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90?mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n?=?63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 10⁴ copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P?<?.001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P?=?.14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P?=?.96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P?=?1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD.     

人疱疹病毒7型被膜蛋白pp85的原核表达及应用

目的构建人疱疹病毒7型(HHV7)被膜蛋白pp85编码基因(ORF U14)的原核表达载体,并进行原核表达。方法应用HHV7标准株Glasgow感染SupT1细胞,PCR技术扩增HHV7ORFU14基因的主要抗原决定簇编码区(328~533AA),目的基因与原核表达载体pThioHis A连接后,转化宿主菌E.coliBL21,IPTG诱导融合蛋白表达,经镍-螯合物琼脂糖树脂柱亲和层析纯化获得重组抗原。重组蛋白电泳后转至PVDF膜,与HHV7阳性血清进行免疫印迹反应。结果DNA序列分析表明,目的基因序列与HHV7标准毒株Glasgow相应序列完全一致,SDS-PAGE可观察到相对分子质量(Mr)为35.7×103融合蛋白的表达,免疫印迹反应显示重组抗原具有较高的特异性。结论HHV7重组抗原具有较好的抗原性,进一步完善后可用于HHV7抗体的检测。     

Quantitation of human herpesvirus-6A, -6B and -7 DNAs in whole blood, mononuclear and polymorphonuclear cell fractions from healthy blood donors

Background

Diagnosis of human herpesvirus-6A (HHV-6A), -6B (HHV-6B) or -7 (HHV-7) infections is often based on the measure of viral load in blood.

Objectives

The aim of this study was to define usual values of HHV-6A, HHV-6B and HHV-7 loads in blood fractions (whole blood [WB], mononuclear cells [PBMCs], polymorphonuclear leukocytes [PMNLs]) of blood donors.

Study design

HHV-6A, HHV-6B and -7 DNAs were quantitated using real-time PCR assays in WB, PBMCs and PMNLs separated on Ficoll or dextran gradients, respectively, for 200 blood donors. Viral loads were expressed as the number of viral genomic copies per million cells (Cop/M) for all fractions, and also per milliliter for WB.

Results

HHV-6B DNA was rarely detected in WB (8%), PBMCs (16.5%), and PMNLs (10.5%), HHV-6A was never detected, whereas HHV-7 DNA was often present in WB (51.5%), PBMCs (62%) and PMNLs (51.5%). Median loads were low with 81 Cop/M in WB, 62 Cop/M in PBMCs and 34.5 Cop/M in PMNLs for HHV-6B, and 129 Cop/M in WB, 225 Cop/M in PBMCs and 62 Cop/M in PMNLs for HHV-7. Viral load expression per million cells and per mL were equivalent. One subject had chromosomally integrated HHV-6 with high viral loads ranging from 2.23 × 10⁶ to 3.21 × 10⁶ Cop/M in all compartments and plasma.

Conclusions

These results allow to propose viral load in WB as a sensitive and suitable marker, with values for healthy subjects at approximately 100 Cop/M for both viruses. The prevalence of chromosomally integrated HHV-6 was 0.5%.     

Association of HHV-6 and HHV-7 reactivation with the development of chronic allograft nephropathy

BackgroundThe long-term effect of HHV-6 and HHV-7 infections on chronic allograft nephropathy (CAN) development after renal transplantation is uncertain.ObjectivesTo determine HHV-6 and HHV-7 reactivation during the post-transplantation period and to evaluate its effect on CAN development in renal transplant patients.Study designEighty-one renal allograft recipients (28 with CAN, 53 with normal transplant function) were studied to determine the frequency of HHV-6 and HHV-7 reactivation during 36.4 ± 7.8 months after renal transplantation using nested PCR. HHV-6 variants were identified using restriction endonuclease analysis. Patients were monitored for the development of CAN.ResultsThe frequency of HHV-6 and/or HHV-7 plasma DNA was significantly higher in CAN patients (25/28, 89.3%) compared to control patients (15/50, 30.0%, p = 0.0001). CAN patients also had an increased incidence of dual active infections (20/25, 80% and 2/15, 13.3%, p = 0.007, respectively). In all 34 HHV-6 positive cases, the HHV-6B variant was identified. The presence of HHV-7 DNA in plasma preceded the presence of HHV-6 DNA. Early development of CAN and graft loss was detected only in patients with simultaneous HHV-6 and HHV-7 plasma DNA.ConclusionsReactivation of HHV-6 and HHV-7 in renal graft recipients is a risk factor for CAN development. The presence of concurrent HHV-6 and HHV-7 DNA in the plasma is an unfavorable prognostic factor.     

Meningitis caused by Rhodotorula rubra in an human immunodeficiency virus infected patient

Rhodotorula spp. are common saprophytes but may be responsible for systemic infections in immunocompromised patients. Meningitis caused by Rhodotorula spp. in human immunodeficiency virus (HIV) infected patients has been reported only rarely. We present a case of meningitis caused by Rhodotorula rubra in HIV infected patient. The presumptive diagnosis of cryptococcal meningitis was made on the basis of India ink preparation, Gram staining and latex agglutination test (LAT) for cryptococcal antigen. The final diagnosis was confirmed by isolation of Rhodotorula rubra from cerebrospinal fluid on culture. LAT was considered false positive. Amphotericin B and 5-fluorocytosine were administered but the patient succumbed to his illness.     

A catastrophic-onset longitudinal myelitis accompanied by bilateral internuclear ophthalmoplegia in a patient with systemic lupus erythematosus

Transverse myelitis (TM) extending from midbrain to the entire spinal cord accompanied by internuclear ophthalmoplegia is extremely rare but cause serious central nervous system complications in patients with systemic lupus erythematosus. We report a case of a 28-yr-old woman with TM extending from the midbrain to the conus medullaris longitudinally and internuclear ophthalmoplegia associated with systemic lupus erythematosus. Her neurological symptoms had an abrupt catastrophic onset and rapidly progressed to respiratory failure within 24 hr. Bilateral internuclear ophthalmoplegia was also followed by TM. Brain MR images showed definite brainstem lesions, which were deeply associated with internuclear ophthalmoplegia, and diffuse signal changes in the whole spinal cord, medulla, pons and midbrain. Clinical improvement of her ophthalmoplegia and of neurological dysfunction of the upper extremities was noted after prompt and aggressive treatment with intravenous pulsed methylprednisolone and cyclophosphamide. However, the neurological dysfunction of the lower limbs and bladder and colon paralysis were almost unchanged until six months passed.     

Herpes simplex virus type-2 ulcers resistant to acyclovir in an AIDS patient — Successful treatment with foscarnet

Summary The case of a 25-year-old homosexual man with large inguinal and perianal ulcers is reported. He had been pretreated extensively with acyclovir. Herpes simplex virus (HSV) was identified in the ulcer tissue byin-situ hybridization. No clinical improvement with acyclovir but a prompt response to foscarnet was noted. In a relapse after 11 weeks an acyclovir-resistant HSV type 2 was isolated. Again, a prompt response to foscarnet was noted. The case is presented in detail, and the clinical impact of resistance of HSV to acyclovir is discussed.Abbreviations HSV Herpes simplex virus - AIDS Acquired Immunodeficiency Syndrome - HIV Human Immunodeficiency Virus - CMV Cytomegalovirus - ESR Erythrocyte sedimentation rate We would like to thank Prof. Dr. K.E. Schneweis from theInstitut für Medizinische Mikrobiologie und Immunologie der Universität Bonn for his kind cooperation and his friendly support.     

Prevalence of human papilloma virus and human herpes virus types 1–7 in human nasal polyposis

This study aimed to investigate the prevalence of human papilloma virus (HPV), herpes simplex virus‐1/‐2 (HSV‐1/‐2), varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus‐6/‐7 (HHV‐6/‐7) in 23 human nasal polyps by applying PCR. Two types of control tissues were used: adjacent inferior/middle turbinates from the patients and inferior/middle turbinates from 13 patients undergoing nasal corrective surgery. EBV was the virus most frequently detected (35%), followed by HPV (13%), HSV‐1 (9%), and CMV (4%). The CMV‐positive polyp was simultaneously positive for HSV‐1. HPV was also detected in the adjacent turbinates (4%) and the adjacent middle turbinate (4%) of one of the HPV‐positive patients. EBV, HSV, and CMV were not detected in the adjacent turbinates of the EBV‐, HSV‐ or CMV‐positive patients. All mucosae were negative for the VZV, HHV‐6, and HHV‐7. This is the first study to deal with the involvement of a comparable group of viruses in human nasal polyposis. The findings support the theory that the presence of viral EBV markedly influences the pathogenesis of these benign nasal tumors. The low incidence of HPV detected confirms the hypothesis that HPV is correlated with infectious mucosal lesions to a lesser extent than it is with proliferative lesions, such as inverted papilloma. The low incidence of HSV‐1 and CMV confirms that these two herpes viruses may play a minor role in the development of nasal polyposis. Double infection with HSV‐1 and CMV may also play a minor, though causative, role in nasal polyp development. VZV and HHV‐6/‐7 do not appear to be involved in the pathogenesis of these mucosal lesions. J. Med. Virol. 81:1613–1619, 2009. © 2009 Wiley‐Liss, Inc.     

Human herpesviruses-6, -7 and -8 in organ transplant recipients

The newer herpesviruses are being increasingly recognized as significant opportunistic pathogens in organ transplant recipients. Published data support the role of human herpesvirus-6 as a potential cause of encephalitis and bone marrow suppression in transplant setting. An association of human herpesvirus-6 with fungal infections and cytomegalovirus infection has also been documented. Human herpesvirus-7 also appears to be an immunomodulatory agent and may facilitate the pathogenicity of cytomegalovirus. Unlike human herpesviruses -6 and -7, human herepsvirus -8 is not ubiquitous; its seroprevalence exhibits wide geographic variation. Human herpesvirus-8 has been causally associated with post-transplant Kaposi's sarcoma. The complete spectrum of pathogenicity and ultimately the effective prophylaxis and management of these viruses has yet to be fully elucidated.     

Concurrent reactivation of varicella zoster virus and herpes simplex virus in an immunocompetent child

Latency within the nervous system is a characteristic feature of herpesviridae infection. It is reactivated by triggering factors such as UV exposure, stress, and trauma. Simultaneous reactivation of herpes simplex and herpes zoster is uncommon, however, an observation provably explained by differences in the triggering mechanism. Concurrent reactivation of herpes simplex virus (HSV) and varicella zoster virus (VZV) is occasionally encountered in immunosuppressed patients; on the other hand, it is rarely reported in immunocompetent individuals. We present the case of an immunocompetent 8-yr-old female patient with concurrent reactivation of HSV on the face and VZV on the right L2 dermatome.     

Visceral leishmaniasis in an HIV-infected patient: Clinical features and response to treatment

Summary We report the case of 43-year-old homosexual patient with HIV infection and a history of travel to the Far East in whom visceral leishmaniasis was the first infectious complication. Symptoms were fever, malaise, weight loss, hepatosplenomegaly, generalized lymphadenopathy, and oral thrush. Laboratory abnormalities included a slight elevation of liver enzymes, impairment of liver function tests, leukocytopenia, anemia, hypergammaglobulinemia, and markedly depressed CD4 + -cell counts. Despite initially successful treatment with pentavalent antimony, a relapse of leishmaniasis occurred after 7 months. Eradication of the infection was not achieved. Treatment was continued as a palliative chronic suppressive treatment with fortnightly pentamidine infusions. The clinical course was complicated by legionella pneumonia and the development of rapidly progressing Kaposi's sarcoma.The case is presented in detail, and the influence of HIV infection on the course of leishmaniasis is discussed.Abbreviations HIV Human Immunodeficiency Virus - AIDS Acquired Immunodeficiency Syndrome - CDC Centers for Disease Control     

Unusual etiology of visual loss in an HIV-infected patient due to endogenous endophthalmitis

Disseminated candidiasis, especially ocular infections such as endophthalmitis, is uncommon in HIV-infected patients. We report a case of candidal endophthalmitis in an HIV-positive non-drug-user patient, following candidemia from a cutaneous abscess at the site of a peripheral catheter. Ocular disease was revealed by a visual decrease in the left eye. DNA analysis using RAPD showed identical patterns of Candida albicans isolated from the skin and eye. Combination therapy with high-dose fluconazole and intravenous amphotericin B was performed. Two intravitreal amphotericin B injections and a vitrectomy were administered because of an amblyopic right eye and severe vitritis. The outcome was favorable without relapse at 18 months.     

Detection of Epstein Barr virus in an hepatic leiomyomatous neoplasm in an adult human immunodeficiency virus 1-infected patient

We report the first case of a human immunodeficiency virus (HIV)-related primary hepatic leiomyoma in an adult patient. The diagnosis was made at autopsy and confirmed by immunohistochemistry. Epstein Barr virus (EBV) was identified in tumour cells by in situ hybridization. Review of the literature revealed 13 cases of visceral myogenic tumours occuring in acquired immunodeficiency syndrome children, and only 2 cases in adults. One was a spinal epidural leiomyoma, the other multiple smooth muscle tumours of the colon and adrenal gland. This is the first report of EBV in smooth muscle neoplastic cells in an HIV-infected adult patient.     

First detection of autochthonous Zika virus transmission in a HIV-infected patient in Rio de Janeiro,Brazil

Since May 2015, Brazil’s Ministry of Health has reported autochthonous transmission of Zika virus (ZIKV) in some states of the country. Simultaneous circulation of Dengue, Chikungunya and ZIKV in the country hinder both the diagnosis and the therapeutic approach of patients seeking care with acute febrile illnesses especially in patients with comorbidities. The association between HIV infection and endemic diseases has been described especially in tropical regions with varying levels of complications, although there has been no report of ZIKV in HIV-infected patients. We report the first autochthonous case of laboratory confirmed ZIKV infection in a HIV-infected patient in Rio de Janeiro, Brazil. He evolved with only mild symptoms and recovered well without major laboratory abnormalities. Phylogenetic analysis of the ZIKV detected in the patient sera clustered within the Asian clade. To the best of our knowledge, this is the first time that Zika virus co-infection is reported in a HIV-infected patient.     

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals,improved with anti-human herpes virus treatment

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.     

Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months.     

Human immunodeficiency virus type 1-anchored CD40 ligand induces secretion of the chemokine interleukin-8 by human primary macrophages

CD40 ligand (CD40L) is mainly expressed in activated CD4⁺T cells and interacts with CD40 on antigen-presenting cells to regulate both humoral and cellular immune responses. We previously reported that CD40L is acquired by emerging HIV-1 particles. Here we demonstrate that both wild-type and a non-functional mutated form of CD40L are incorporated within HIV-1. Importantly, we show that wild-type CD40L remains functional since CD40L-bearing virions mediate NF-κB activation in a CD40-expressing reporter cell line and induce secretion of the chemokine IL-8 by monocyte-derived macrophages. These results suggest a possible means exploited by HIV-1 to attract susceptible target cells to the site of infection, a process that might promote viral dissemination.