Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient

Dhenni, Rama; Karyanti, Mulya Rahma; Putri, Nina Dwi; Yohan, Benediktus; Yudhaputri, Frilasita A.; Ma’roef, Chairin Nisa; Fadhilah, Araniy; Perkasa, Aditya; Restuadi, Restuadi; Trimarsanto, Hidayat; Mangunatmadja, Irawan; Ledermann, Jeremy P.; Rosenberg, Ronald; Powers, Ann M.; Myint, Khin Saw Aye; Sasmono, R. Tedjo

doi:10.1371/journal.pntd.0006198

Cited by 17 publications

(17 citation statements)

References 48 publications

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“…sequence for DENV-3 and two studies that reported partial E-NS1 sequences for DENV-2, have examined the genetic characteristics of neurotropic DENV. All of these DENV were isolated from CSF samples [8,[42][43][44][45]. To our knowledge, this is the first report to describe the complete genome and the molecular and virological characteristics of DENV-2 isolated from CSF samples from fatal and non-fatal dengue case-patients with neurological manifestations.…”

Section: Plos Onementioning

confidence: 93%

“…To our knowledge, this is the first report to describe the complete genome and the molecular and virological characteristics of DENV-2 isolated from CSF samples from fatal and non-fatal dengue case-patients with neurological manifestations. Compared with other dengue serotypes, DENV-2 and DENV-3 appear to be more frequently associated with encephalitis and other neurological manifestations, regardless of whether it is primary or secondary infections [43,45]. In a meta-analysis examining the severity of dengue during primary or secondary infection with different DENV serotypes, secondary infections with DENV-2 were reported to be associated with severe cases [46].…”

Section: Plos Onementioning

confidence: 99%

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Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

et al. 2020

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Dengue virus (DENV) infection remains a major public health concern in many parts of the world, including Southeast Asia and the Americas. Sri Lanka experienced its largest dengue outbreak in 2017. Neurological symptoms associated with DENV infection have increasingly been reported in both children and adults. Here, we characterize DENV type 2 (DENV-2) strains, which were isolated from cerebrospinal fluid (CSF) and/or serum of patients with dengue encephalitis. Acute serum and CSF samples from each patient were subjected to dengue-specific non-structural protein 1 (NS1) antigen test, IgM and IgG enzyme-linked immunosorbent assay (ELISA), virus isolation, conventional and real-time polymerase chain reaction (PCR), and next-generation sequencing (NGS). Among the 5 dengue encephalitis patients examined, 4 recovered and 1 died. DENV-2 strains were isolated from serum and/or CSF samples of 3 patients. The highest viral genome levels were detected in the CSF and serum of the patient who succumbed to the illness. A phylogenetic tree revealed that the DENV-2 isolates belonged to a new clade of cosmopolitan genotype and were genetically close to strains identified in China, South Korea, Singapore, Malaysia, Thailand, and the Philippines. According to the NGS analysis, greater frequencies of nonsynonymous and synonymous mutations per gene were identified in the nonstructural genes. The full genomes of serum-and CSF-derived DENV-2 from the same patient shared 99.7% similarity, indicating that the virus spread across the blood-brain barrier. This is the first report to describe neurotropic DENV-2 using whole-genome analysis and to provide the clinical, immunological, and virological characteristics of dengue encephalitis patients during a severe dengue outbreak in Sri Lanka in 2017.

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Section: Plos Onementioning

confidence: 93%

Section: Plos Onementioning

confidence: 99%

Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

et al. 2020

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“…CSF specimens were inoculated onto African green monkey kidney Vero cells as previously described [18]. Cells were observed daily for cytopathic effect.…”

Section: Virus Isolationmentioning

confidence: 99%

Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia

et al. 2018

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Central nervous system (CNS) viral infections are important causes of morbidity and mortality worldwide but the systematic survey of patients admitted to hospitals with CNS infections in many countries, including Indonesia, is limited. To obtain more information regarding the causes of CNS infections in Indonesia, this study was performed to detect and identify viral agents associated with CNS infections amongst in-patients at a referral hospital in Manado, North Sulawesi, Indonesia. Adult patients admitted to R.D. Kandou General Hospital with presumed CNS infection were enrolled. Cerebrospinal fluid, serum, and throat swab samples were collected and tested using molecular, serological, and virus isolation assays. A confirmed viral etiology was established in three and a probable/possible in 11 out of 74 patients. The most common was herpes simplex virus 1 (7/74, 9.5%), followed by Epstein-Barr virus (2/74, 2.7%), cytomegalovirus (1/74, 1.4%), enterovirus D68 (1/74, 1.4%), rhinovirus A (1/74, 1.4%), dengue virus (1/64, 1.6%), and Japanese encephalitis virus (1/64, 1.6%). There were 20 fatal cases (27.0%) during hospitalization in which eight were associated with viral causes. We identified herpes simplex virus 1 as the most common cause of CNS infection among adults in North Sulawesi with most of the cases remaining undiagnosed. Our study highlights the challenges in establishing the etiology of viral CNS infections and the importance of using a wide range of molecular and serological detection methods to identify CNS viruses.

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“…CSF proteomics has previously identified clinically useful protein biomarkers such as amyloid precursor protein and cell adhesion molecules in PHH 17,27 . DNA or RNA sequencing from CSF has been widely used to study infectious diseases 28,29 . Because disease pathogenesis involves the combinatorial interaction of elements within the proteome, transcriptome, and environmental factors 30,31 Although there is a rapid progression of immunologic competence after birth, the innate immune system is the primary active defense for infants less than 3 months of age, since they lack the antigenic experience that informs acquired immunity.…”

Section: Discussionmentioning

confidence: 99%

Central nervous system immune response in postinfectious hydrocephalus

Isaacs

Morton

Movassagh

et al. 2020

Preprint

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Inflammation following neonatal infection is a dominant cause of childhood hydrocephalus in the developing world. Understanding this complex inflammatory response is critical for the development of preventive therapies. In 100 African hydrocephalic infants ≤3 months of age, with and without a history of infection, we elucidated the biological pathways that account for this inflammatory response. We integrated proteomics and RNA sequencing in cerebrospinal fluid, identifying gene pathways involving neutrophil, interleukin (4, 12, and 13) and interferon activity associated with this condition. These findings are required to develop strategies to reduce the risk of hydrocephalus during treatment of infection.

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Isolation and complete genome analysis of neurotropic dengue virus serotype 3 from the cerebrospinal fluid of an encephalitis patient

Cited by 17 publications

References 48 publications

Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

Detection of central nervous system viral infections in adults in Manado, North Sulawesi, Indonesia

Central nervous system immune response in postinfectious hydrocephalus

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