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Mierzewska-Schmidt M, Piwowarczyk A, Szymanska K, Ciaston M, Podsiadly E, Przybylski M, Pagowska-Klimek I. Fatal Fulminant Epstein-Barr Virus (EBV) Encephalitis in Immunocompetent 5.5-Year-Old Girl-A Case Report with the Review of Diagnostic and Management Dilemmas. Biomedicines 2024; 12:2877. [PMID: 39767783 PMCID: PMC11673975 DOI: 10.3390/biomedicines12122877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/12/2024] [Accepted: 12/13/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Epstein-Barr virus (EBV) usually causes mild, self-limiting, or asymptomatic infection in children, typically infectious mononucleosis. The severe course is more common in immunocompromised patients. Neurological complications of primary infection, reactivation of the latent infection, or immune-mediated are well-documented. However, few published cases of fatal EBV encephalitis exist. Case presentation We report a case of a 5.5-year-old immunocompetent girl with fulminant EBV encephalitis fulfilling the criteria for the recently proposed subtype Acute Fulminant Cerebral Edema: (AFCE). The child presented with fever, vomiting, altered mental status, and ataxia. Her initial brain CT (computed tomography) scan was normal. On day 2 she developed refractory status epilepticus requiring intubation, ventilation, and sedation for airway protection and seizure control. Magnetic resonance imaging (MRI) scan showed cytotoxic brain edema. Despite intensive treatment, including acyclovir, ceftriaxone, hyperosmotic therapy (3% NaCl), intravenous immunoglobulins (IVIG), corticosteroids, as well as supportive management, on day 5 she developed signs of impending herniation. Intensification of therapy (hyperventilation, deepening sedation, mannitol) was ineffective, and a CT scan demonstrated generalized brain edema with tonsillar herniation. EBV primary infection was confirmed by serology and qPCR in blood samples and post-mortem brain tissue. An autopsy was consistent with the early phase of viral encephalitis. Conclusions This case confirms that normal or non-specific CT and MRI scans do not exclude encephalitis diagnosis if clinical presentation fulfills the diagnostic criteria. The implementation of prophylactic anticonvulsants could improve outcomes. Intracranial pressure (ICP) monitoring should be considered in AFCE for better ICP management. Decompressive craniectomy might be a life-saving option in refractory cases. An encephalitis management algorithm is proposed.
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Affiliation(s)
- Magdalena Mierzewska-Schmidt
- Department of Pediatric Anesthesiology and Intensive Therapy, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Anna Piwowarczyk
- Department of Pediatrics with Clinical Assessment Unit, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Krystyna Szymanska
- Department of Pediatric Neurology and Rare Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Michal Ciaston
- Department of Pediatric Radiology, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Edyta Podsiadly
- Laboratory of Microbiology, University Center of Laboratory Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Dental Microbiology, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Maciej Przybylski
- Chair and Department of Medical Microbiology, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Izabela Pagowska-Klimek
- Department of Pediatric Anesthesiology and Intensive Therapy, Medical University of Warsaw, 02-091 Warsaw, Poland
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Wang J, Li M, Zhu J, Cheng L, Kong P. Mycobacterium tuberculosis combine with EBV infection in severe adult meningoencephalitis: a rare case reports and literature review. Front Cell Infect Microbiol 2024; 14:1361119. [PMID: 39469454 PMCID: PMC11513340 DOI: 10.3389/fcimb.2024.1361119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 08/30/2024] [Indexed: 10/30/2024] Open
Abstract
Background Tuberculous meningitis (TBM) with adults Epstein-Barr (EB) virus encephalitis is a very rare infectious disease, with a high mortality and disability. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is highly diagnostic. We report on a case of severe meningoencephalitis caused by co-infection with mycobacterium tuberculosis and EB virus. Brain MRI indicated a parenchyma lesion in the brain. mNGS of CSF indicated Mycobacterium tuberculosis and EB virus amplification, positive serum EB virus IgG antibodies, and improved symptoms after anti-tuberculosis and antiviral treatment. A re-examination of the brain MRI revealed that the significantly absorption of the lesions. Case report A 49-year-old male patient presented with a chief complaint of headache and fever with consciousness disturbance. The brain magnetic resonance imaging showed a lesions in the right parenchymal brain with uneven enhancement, accompanied by significantly increased intracranial pressure, elevated CSF cell count and protein levels, as well as notably decreased glucose and chloride levels. mNGS of CSF showed the coexistence of Mycobacterium tuberculosis and EBV. The patient was diagnosed as TBM with EBV encephalitis. The patient's symptoms gradually improved with the active administration of anti-tuberculosis combined with antiviral agents, the use of hormones to reduce inflammatory reaction, dehydration to lower intracranial pressure, and intrathecal injection. Subsequent follow-up brain magnetic resonance imaging indicated significant absorption of the lesions, along with a marked decrease in CSF count and protein levels, as well as obvious increase in glucose and chloride levels. Conclusion TBM associated with adult EBV encephalitis is extremely rare. The disease's early stages are severe and have a high fatality rate. A prompt and accurate diagnosis is particularly important. NGS of CSF is of great value for early diagnosis.
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Affiliation(s)
- Jian Wang
- Department of Neurology, Affiliated Aerospace Hospital of Zunyi Medical University, Zunyi, Guizhou, China
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Trujillo-Gómez J, Navarro CE, Atehortúa-Muñoz S, Florez ID. Acute infections of the central nervous system in children and adults: diagnosis and management. Minerva Med 2024; 115:476-502. [PMID: 39376101 DOI: 10.23736/s0026-4806.24.09097-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
Central nervous system infections are due to different microorganisms such as viruses, bacteria, mycobacteria, fungi, amoebas, and other parasites. The etiology depends on multiple risk factors, and it defines the infection location because some microorganisms prefer meninges, brain tissue, cerebellum, brain stem or spinal cord. The microorganisms induce diseases in the nervous system through direct invasion, neurotoxin production, and the triggered immune response. To determine the infection etiology, there are several diagnostic tests which may be conducted with cerebrospinal fluid, blood, respiratory and stool samples. These tests include but are not limited to direct microscopic examination of the sample, stains, cultures, antigenic tests, nucleic acid amplification tests, metagenomic next-generation sequencing, immunologic biomarker and neuroimaging, especially contrast-enhanced magnetic resonance imaging. The treatment may consist of specific antimicrobial treatment and supportive standard care. Since viruses have no specific antiviral treatment, antimicrobial treatment is mainly targeted at non-viral infections. This article will focus on diagnosis and treatment of acute acquired infections of the central nervous system beyond the neonatal period. The discussion defines the disease, provides the clinical presentation, explains the etiology and risk factors, and briefly mentions potential complications. This updated review aims to provide the reader with all the elements needed to adequately approach a patient with a central nervous system infection. Mycobacterium tuberculosis infection, Cryptococcus spp. infection and vaccines are not within the scope of this article.
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Affiliation(s)
- Juliana Trujillo-Gómez
- Hospital General de Medellín, Medellín, Colombia
- School of Medicine, University of Antioquia, Medellín, Colombia
| | - Cristian E Navarro
- School of Medicine, University of Antioquia, Medellín, Colombia
- Grupo de Investigación, ESE Hospital Emiro Quintero Cañizares, Ocaña, Colombia
| | - Santiago Atehortúa-Muñoz
- Hospital Pablo Tobón Uribe, Medellín, Colombia
- Clínica Universitaria Bolivariana, Medellín, Colombia
| | - Ivan D Florez
- Department of Pediatrics, University of Antioquia, Medellín, Colombia -
- School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
- Pediatric Intensive Care Unit, Clínica Las Américas AUNA, Medellín, Colombia
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de Melo SA, Pinto SD, Ferreira EDS, Brotas R, Marinho EPM, da Silva VA, Monte RL, Feitoza PVS, Reis MF, Almeida TVR, Ferreira LCDL, Bastos MDS. Molecular diagnosis of opportunistic infections in the central nervous system of HIV-infected adults in Manaus, Amazonas. Front Med (Lausanne) 2024; 10:1298435. [PMID: 38264048 PMCID: PMC10803427 DOI: 10.3389/fmed.2023.1298435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 12/22/2023] [Indexed: 01/25/2024] Open
Abstract
Background Opportunistic infections in the central nervous system (CNS) of people with HIV/AIDS (PLWHA) remain significant contributors to morbidity and mortality, especially in resource-limited scenarios. Diagnosing these infections can be challenging, as brain imaging is non-specific and expensive. Therefore, molecular analysis of cerebrospinal fluid (CSF) may offer a more accurate and affordable method for diagnosing pathogens. Methods We conducted extensive real-time PCR testing (qPCR) on CSF to evaluate etiological agents in PLWHA with neurological manifestations. Primers targeting DNA from specific pathogens, including cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), John Cunningham virus (JCV), Toxoplasma gondii, and human T-lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2), were used. Results Cerebrospinal fluid samples revealed 90 pathogens (36.7%). Toxoplasma gondii was the most frequently detected pathogen, found in 22 samples (30.5%). Other pathogens included Cryptococcus sp. (7.7%), EBV (5.3%), CMV, VZV, and JCV (4.0% each). Conclusion Despite antiretroviral therapy and medical follow-up, opportunistic central nervous system infections remain frequent in PLWHA. Herpesviruses are commonly detected, but T. gondii is the most prevalent opportunistic pathogen in our study population. Therefore, molecular diagnosis is a crucial tool for identifying opportunistic infections, even in patients undergoing treatment.
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Affiliation(s)
| | | | | | - Reinan Brotas
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | | | | | - Rossiclea Lins Monte
- Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil
| | | | | | - Taynná V. Rocha Almeida
- Departamento de Formação em Emergências em Saúde Pública, Ministério da Saúde, Brasília, Distrito Federal, Brazil
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Cho SY, Jang BH, Seo JW, Kim SW, Lim KJ, Lee HY, Kim DJ. Transverse myelitis caused by herpes zoster following COVID-19 vaccination: A case report. World J Clin Cases 2023; 11:1419-1425. [PMID: 36926132 PMCID: PMC10013101 DOI: 10.12998/wjcc.v11.i6.1419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 01/17/2023] [Accepted: 02/03/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased.
CASE SUMMARY This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/ AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6–T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17.
CONCLUSION HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.
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Affiliation(s)
- Su-Yeon Cho
- Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju 61453, South Korea
| | - Bo-Hyun Jang
- Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju 61453, South Korea
| | - Jun-Won Seo
- Department of Internal Medicine, Chosun University, College of Medicine, Gwangju 61453, South Korea
| | - Suk-Whee Kim
- Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju 61453, South Korea
| | - Kyung-Joon Lim
- Department of Anesthesiology and Pain Medicine, Chosun University, College of Medicine, Gwangju 61453, South Korea
| | - Hyun-Young Lee
- Department of Anesthesiology and Pain Medicine, Chosun University, College of Medicine, Gwangju 61453, South Korea
| | - Dong-Joon Kim
- Department of Anesthesiology and Pain Medicine, Chosun University, College of Medicine, Gwangju 61453, South Korea
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New Insights into the Molecular Interplay between Human Herpesviruses and Alzheimer’s Disease—A Narrative Review. Brain Sci 2022; 12:brainsci12081010. [PMID: 36009073 PMCID: PMC9406069 DOI: 10.3390/brainsci12081010] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/24/2022] [Accepted: 07/28/2022] [Indexed: 12/15/2022] Open
Abstract
Human herpesviruses (HHVs) have been implicated as possible risk factors in Alzheimer’s disease (AD) pathogenesis. Persistent lifelong HHVs infections may directly or indirectly contribute to the generation of AD hallmarks: amyloid beta (Aβ) plaques, neurofibrillary tangles composed of hyperphosphorylated tau proteins, and synaptic loss. The present review focuses on summarizing current knowledge on the molecular mechanistic links between HHVs and AD that include processes involved in Aβ accumulation, tau protein hyperphosphorylation, autophagy, oxidative stress, and neuroinflammation. A PubMed search was performed to collect all the available research data regarding the above mentioned mechanistic links between HHVs and AD pathology. The vast majority of research articles referred to the different pathways exploited by Herpes Simplex Virus 1 that could lead to AD pathology, while a few studies highlighted the emerging role of HHV 6, cytomegalovirus, and Epstein–Barr Virus. The elucidation of such potential links may guide the development of novel diagnostics and therapeutics to counter this devastating neurological disorder that until now remains incurable.
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Trabelsi B, Ben Rhaiem R, Ben Rabeh R, Ben Ahmed S, Ben Ali M. Epstein-Barr virus-associated encephalitis during pregnancy: a diagnostic and therapeutic challenge. Acta Neurol Belg 2022:10.1007/s13760-022-01986-1. [PMID: 35653058 DOI: 10.1007/s13760-022-01986-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 05/23/2022] [Indexed: 11/27/2022]
Affiliation(s)
- Becem Trabelsi
- Anesthesiology and Intensive Care Unit, Taher Maamouri Teaching Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Mrezga, 8000, Nabeul, Tunisia.
| | - Riadh Ben Rhaiem
- Anesthesiology and Intensive Care Unit, Taher Maamouri Teaching Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Mrezga, 8000, Nabeul, Tunisia
| | - Rania Ben Rabeh
- Department of Pediatrics C, Bechir Hamza Children Hospital of Tunis, Faculty of Medicine of Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Sameh Ben Ahmed
- Anesthesiology and Intensive Care Unit, Taher Maamouri Teaching Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Mrezga, 8000, Nabeul, Tunisia
| | - Mechaal Ben Ali
- Anesthesiology and Intensive Care Unit, Taher Maamouri Teaching Hospital, Faculty of Medicine of Tunis, University Tunis El Manar, Mrezga, 8000, Nabeul, Tunisia
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Maes L, Theunissen K, Schepers S, Indesteege I, Delmotte K. Acute autonomic dysregulation due to HHV-6 encephalitis in an immunocompromised patient: a case report and literature review. Acta Neurol Belg 2022; 122:583-585. [PMID: 35349121 DOI: 10.1007/s13760-021-01828-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/21/2021] [Indexed: 02/03/2023]
Abstract
Human herpesvirus-6 (HHV-6), in particularly HHV-6B, can reactivate in immunocompromised patients. Especially after stem cell transplantation, reactivation of HHV-6 can cause complications, such as limbic encephalitis. We present a case of a 61-year-old man with B-cell non-Hodgkin lymphoma. He presented with subacute lethargy, confusion and hyperhidrosis. Following this, we will give a short review of the literature considering clinical and technical features as well as treatment options.
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Affiliation(s)
- Louise Maes
- Department of Neurology, Jessa Hospital, Stadsomvaart 11, B-3500, Hasselt, Belgium.
| | | | | | | | - Koen Delmotte
- Department of Neurology, Jessa Hospital, Stadsomvaart 11, B-3500, Hasselt, Belgium
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Krett JD, Beckham JD, Tyler KL, Piquet AL, Chauhan L, Wallace CJ, Pastula DM, Kapadia RK. Neurology of Acute Viral Infections. Neurohospitalist 2022; 12:632-646. [PMID: 36147750 PMCID: PMC9485684 DOI: 10.1177/19418744221104778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
As specialists in acute neurology, neurohospitalists are often called upon to diagnose and manage acute viral infections affecting the nervous system. In this broad review covering the neurology of several acute viral infections, our aim is to provide key diagnostic and therapeutic pearls of practical use to the busy neurohospitalist. We will review acute presentations, diagnosis, and treatment of human herpesviruses, arboviruses, enteroviruses, and some vaccine-preventable viruses. The neurological effects of coronaviruses, including COVID-19, are not covered in this review.
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Affiliation(s)
- Jonathan D Krett
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
| | - J David Beckham
- Department of Neurology and Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Neurosciences Center, Aurora, CO, USA
- Departments of Immunology & Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA
| | - Kenneth L Tyler
- Department of Neurology and Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Neurosciences Center, Aurora, CO, USA
- Departments of Immunology & Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA
| | - Amanda L Piquet
- Department of Neurology and Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Neurosciences Center, Aurora, CO, USA
| | - Lakshmi Chauhan
- Department of Neurology and Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Neurosciences Center, Aurora, CO, USA
| | - Carla J Wallace
- Department of Radiology, University of Calgary, Calgary, AB, Canada
| | - Daniel M Pastula
- Department of Neurology and Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Neurosciences Center, Aurora, CO, USA
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA
| | - Ronak K Kapadia
- Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
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Gao Y, Cheng J, Xu X, Li X, Zhang J, Ma D, Jiang G, Liao Y, Fan S, Niu Z, Yue R, Chang P, Zeng F, Duan S, Meng Z, Xu X, Li X, Li D, Yu L, Ping L, Zhao H, Guo M, Wang L, Wang Y, Zhang Y, Li Q. HSV-1 Infection of Epithelial Dendritic Cells Is a Critical Strategy for Interfering with Antiviral Immunity. Viruses 2022; 14:1046. [PMID: 35632787 PMCID: PMC9147763 DOI: 10.3390/v14051046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/06/2022] [Accepted: 05/12/2022] [Indexed: 11/17/2022] Open
Abstract
Herpes simplex virus type 1 (HSV-1), an α subgroup member of the human herpesvirus family, infects cells via the binding of its various envelope glycoproteins to cellular membrane receptors, one of which is herpes virus entry mediator (HVEM), expressed on dendritic cells. Here, HVEM gene-deficient mice were used to investigate the immunologic effect elicited by the HSV-1 infection of dendritic cells. Dendritic cells expressing the surface marker CD11c showed an abnormal biological phenotype, including the altered transcription of various immune signaling molecules and inflammatory factors associated with innate immunity after viral replication. Furthermore, the viral infection of dendritic cells interfered with dendritic cell function in the lymph nodes, where these cells normally play roles in activating the T-cell response. Additionally, the mild clinicopathological manifestations observed during the acute phase of HSV-1 infection were associated with viral replication in dendritic cells.
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Affiliation(s)
- Yang Gao
- Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming 650000, China; (X.X.); (X.L.); (J.Z.); (D.M.); (G.J.); (Y.L.); (S.F.); (Z.N.); (R.Y.); (P.C.); (F.Z.); (S.D.); (Z.M.); (X.X.); (X.L.); (D.L.); (L.Y.); (L.P.); (H.Z.); (M.G.); (L.W.); (Y.W.); (Y.Z.); (Q.L.)
| | - Jishuai Cheng
- Yunnan Key Laboratory of Vaccine Research and Development for Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming 650000, China; (X.X.); (X.L.); (J.Z.); (D.M.); (G.J.); (Y.L.); (S.F.); (Z.N.); (R.Y.); (P.C.); (F.Z.); (S.D.); (Z.M.); (X.X.); (X.L.); (D.L.); (L.Y.); (L.P.); (H.Z.); (M.G.); (L.W.); (Y.W.); (Y.Z.); (Q.L.)
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Zheng H, Savitz J. Effect of Cytomegalovirus Infection on the Central Nervous System: Implications for Psychiatric Disorders. Curr Top Behav Neurosci 2022; 61:215-241. [PMID: 35505056 DOI: 10.1007/7854_2022_361] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cytomegalovirus (CMV) is a common herpesvirus that establishes lifelong latent infections and interacts extensively with the host immune system, potentially contributing to immune activation and inflammation. Given its proclivity for infecting the brain and its reactivation by inflammatory stimuli, CMV is well known for causing central nervous system complications in the immune-naïve (e.g., in utero) and in the immunocompromised (e.g., in neonates, individuals receiving transplants or cancer chemotherapy, or people living with HIV). However, its potentially pathogenic role in diseases that are characterized by more subtle immune dysregulation and inflammation such as psychiatric disorders is still a matter of debate. In this chapter, we briefly summarize the pathogenic role of CMV in immune-naïve and immunocompromised populations and then review the evidence (i.e., epidemiological studies, serological studies, postmortem studies, and recent neuroimaging studies) for a link between CMV infection and psychiatric disorders with a focus on mood disorders and schizophrenia. Finally, we discuss the potential mechanisms through which CMV may cause CNS dysfunction in the context of mental disorders and conclude with a summary of the current state of play as well as potential future research directions in this area.
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Affiliation(s)
- Haixia Zheng
- Laureate Institute for Brain Research, Tulsa, OK, USA.
| | - Jonathan Savitz
- Laureate Institute for Brain Research, Tulsa, OK, USA.,Oxley College of Health Sciences, The University of Tulsa, Tulsa, OK, USA
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Šudomová M, Berchová-Bímová K, Mazurakova A, Šamec D, Kubatka P, Hassan STS. Flavonoids Target Human Herpesviruses That Infect the Nervous System: Mechanisms of Action and Therapeutic Insights. Viruses 2022; 14:v14030592. [PMID: 35336999 PMCID: PMC8949561 DOI: 10.3390/v14030592] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 03/08/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Abstract
Human herpesviruses (HHVs) are large DNA viruses with highly infectious characteristics. HHVs can induce lytic and latent infections in their host, and most of these viruses are neurotropic, with the capacity to generate severe and chronic neurological diseases of the peripheral nervous system (PNS) and central nervous system (CNS). Treatment of HHV infections based on strategies that include natural products-derived drugs is one of the most rapidly developing fields of modern medicine. Therefore, in this paper, we lend insights into the recent advances that have been achieved during the past five years in utilizing flavonoids as promising natural drugs for the treatment of HHVs infections of the nervous system such as alpha-herpesviruses (herpes simplex virus type 1, type 2, and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein–Barr virus and Kaposi sarcoma-associated herpesvirus). The neurological complications associated with infections induced by the reviewed herpesviruses are emphasized. Additionally, this work covers all possible mechanisms and pathways by which flavonoids induce promising therapeutic actions against the above-mentioned herpesviruses.
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Affiliation(s)
- Miroslava Šudomová
- Museum of Literature in Moravia, Klášter 1, 664 61 Rajhrad, Czech Republic;
| | - Kateřina Berchová-Bímová
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 16500 Prague, Czech Republic;
| | - Alena Mazurakova
- Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Dunja Šamec
- Department of Food Technology, University Center Koprivnica, University North, Trga Dr. Žarka Dolinara 1, 48 000 Koprivnica, Croatia;
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Sherif T. S. Hassan
- Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 16500 Prague, Czech Republic;
- Correspondence: ; Tel.: +420-774-630-604
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Nguyen AM, Decker JA, Dupuis JE, Little AA, Ottenhoff LD, Rajajee V, Sheehan KM, Williamson CA. A 57 Year-Old Man With HIV Presenting With Severe Headache and Progressive Weakness. Neurohospitalist 2022; 12:171-176. [PMID: 34950409 PMCID: PMC8689552 DOI: 10.1177/1941874420980630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Andrew M. Nguyen
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
| | - Jenna A. Decker
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
| | - Janae E. Dupuis
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
| | - Ann A. Little
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA
| | | | - Venkatakrishna Rajajee
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA,Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA
| | - Kyle M. Sheehan
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA,Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA
| | - Craig A. Williamson
- Department of Neurology, University of Michigan, Ann Arbor, MI, USA,Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA,Craig A. Williamson, Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
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14
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Leon LL, Lima RGD, Boffi LC, Bindilatti RN, Garlipp CR, Costa SCB, Bonon SHA. Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018. Rev Soc Bras Med Trop 2021; 54:e0127. [PMID: 34787257 PMCID: PMC8582960 DOI: 10.1590/0037-8682-0127-2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/31/2021] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION: Herpesviruses, enteroviruses, and arboviruses are important because of their clinical relevance and ability to cause meningitis, encephalitis, meningoencephalitis, and other diseases. The clinical virology associated with diagnostic technologies can reduce the morbidity and mortality of such neurological manifestations. Here we aimed to identify the genomes of agents that cause neurological syndromes in cerebrospinal fluid (CSF) samples from patients with suspected nervous system infections admitted to the University Hospital of the University of Campinas, São Paulo, Brazil, in 2017-2018. METHODS: CSF samples collected from adult patients with neurological syndrome symptoms and negative CSF culture results were analyzed using polymerase chain reaction (PCR), reverse transcriptase-PCR, and real-time PCR, and their results were compared with their clinical symptoms. One CSF sample was obtained from each patient. RESULTS: Viral genomes were detected in 148/420 (35.2%) CSF samples: one of 148 (0.2%) was positive for herpes simplex virus-1; two (0.5%) for herpes simplex virus-2; eight (1.9%) for varicella-zoster virus; four (1%) for Epstein-Barr virus; one (0.2%) for cytomegalovirus; 32 (7.6%) for human herpesvirus-6; 30 (7.1%) for non-polio enterovirus; 67 (16.0%) for dengue virus, three (0.7%) for yellow fever virus, and 21 (5%) for Zika virus. CONCLUSIONS: The viral genomes were found in 35.2% of all analyzed samples, showing the high prevalence of viruses in the nervous system and the importance of using a nucleic acid amplification test to detect viral agents in CSF samples.
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Affiliation(s)
- Lucas Lopes Leon
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Rodrigo Gonçalves de Lima
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Lídia Cristian Boffi
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Raissa Nery Bindilatti
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Célia Regina Garlipp
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Patologia Clínica, Campinas, SP, Brasil
| | - Sandra Cecília Botelho Costa
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Sandra Helena Alves Bonon
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
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15
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Schreiber-Stainthorp W, Solomon J, Lee JH, Castro M, Shah S, Martinez-Orengo N, Reeder R, Maric D, Gross R, Qin J, Hagen KR, Johnson RF, Hammoud DA. Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection. Nat Commun 2021; 12:2855. [PMID: 34001896 PMCID: PMC8129091 DOI: 10.1038/s41467-021-23088-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 04/13/2021] [Indexed: 02/03/2023] Open
Abstract
Ebola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood-brain barrier disruption, likely related to high cytokine levels and endothelial viral infection, with extravasation of fluid, Gadolinium-based contrast material and albumin into the extracellular space. Increased glucose metabolism is also present compared to the baseline, especially in the deep gray matter and brainstem. This regional hypermetabolism corresponds with mild neuroinflammation, sporadic neuronal infection and apoptosis, as well as increased GLUT3 expression, consistent with increased neuronal metabolic demands. Neuroimaging changes are associated with markers of disease progression including viral load and cytokine/chemokine levels. Our results provide insight into the pathophysiology of CNS involvement with EBOV and may help assess vaccine/treatment efficacy in real time.
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Affiliation(s)
- William Schreiber-Stainthorp
- Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA
| | - Jeffrey Solomon
- Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Ji Hyun Lee
- Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Marcelo Castro
- Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Swati Shah
- Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA
| | - Neysha Martinez-Orengo
- Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA
| | - Rebecca Reeder
- Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Dragan Maric
- Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA
| | - Robin Gross
- Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Jing Qin
- Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA
| | - Katie R Hagen
- Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Reed F Johnson
- Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA
| | - Dima A Hammoud
- Hammoud Laboratory, Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA.
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16
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Cheng H, Chen D, Peng X, Wu P, Jiang L, Hu Y. Clinical characteristics of Epstein-Barr virus infection in the pediatric nervous system. BMC Infect Dis 2020; 20:886. [PMID: 33238935 PMCID: PMC7691062 DOI: 10.1186/s12879-020-05623-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 11/17/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND To investigate the clinical characteristics of Epstein-Barr virus (EBV) infection in the pediatric nervous system (NS). METHODS We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019. RESULTS EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0-4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain-Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. CONCLUSION There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.
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Affiliation(s)
- Huan Cheng
- Department of Neurology, Children’s Hospital of Chongqing Medical University, No.136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014 China
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China
- China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Doudou Chen
- Department of Neurology, Children’s Hospital of Chongqing Medical University, No.136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014 China
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China
- China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Xiaoling Peng
- Division of Science and Technology, Beijing Normal University-Hongkong Baptist University United International College, Zhuhai, China
| | - Peng Wu
- Department of Neurology, Children’s Hospital of Chongqing Medical University, No.136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014 China
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China
- China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Li Jiang
- Department of Neurology, Children’s Hospital of Chongqing Medical University, No.136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014 China
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China
- China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Yue Hu
- Department of Neurology, Children’s Hospital of Chongqing Medical University, No.136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014 China
- Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China
- National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, China
- China International Science and Technology Cooperation base of Child Development and Critical Disorders, Chongqing, China
- Chongqing Key Laboratory of Pediatrics, Chongqing, China
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17
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Clinical spectrum and prognosis of neurological complications of reactivated varicella-zoster infection: the role of immunosuppression. J Neurovirol 2020; 26:696-703. [PMID: 32696182 DOI: 10.1007/s13365-020-00872-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 06/08/2020] [Accepted: 06/15/2020] [Indexed: 12/26/2022]
Abstract
Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74-10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor.
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18
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Xu X, Zhang Y, Li Q. Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development. Rev Med Virol 2019; 29:e2054. [PMID: 31197909 PMCID: PMC6771534 DOI: 10.1002/rmv.2054] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 04/03/2019] [Accepted: 04/27/2019] [Indexed: 12/15/2022]
Abstract
Herpes simplex virus (HSV) can cause oral or genital ulcerative lesions and even encephalitis in various age groups with high infection rates. More seriously, HSV may lead to a wide range of recurrent diseases throughout a lifetime. No vaccines against HSV are currently available. The accumulated clinical research data for HSV vaccines reveal that the effects of HSV interacting with the host, especially the host immune system, may be important for the development of HSV vaccines. HSV vaccine development remains a major challenge. Thus, we focus on the research data regarding the interactions of HSV and host immune cells, including dendritic cells (DCs), innate lymphoid cells (ILCs), macrophages, and natural killer (NK) cells, and the related signal transduction pathways involved in immune evasion and cytokine production. The aim is to explore possible strategies to develop new effective HSV vaccines.
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Affiliation(s)
- Xingli Xu
- Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical SciencesPeking Union Medical CollegeKunmingChina
| | - Ying Zhang
- Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical SciencesPeking Union Medical CollegeKunmingChina
| | - Qihan Li
- Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical SciencesPeking Union Medical CollegeKunmingChina
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